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Charlotte Brinck H, Lene H, Tom D, Wilhelm S, Troels Krarup H, Steffen T, Jakob Appel Ø. MASP-2 deficiency does not prevent the progression of diabetic kidney disease in a mouse model of type 1 diabetes. Scand J Immunol 2024; 99:e13348. [PMID: 39008346 DOI: 10.1111/sji.13348] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 11/14/2023] [Accepted: 12/06/2023] [Indexed: 07/16/2024]
Abstract
Mannan-binding lectin (MBL) initiates the lectin pathway of complement and has been linked to albuminuria and mortality in diabetes. We hypothesize that MBL-associated serine protease 2 (MASP-2) deficiency will protect against diabetes-induced kidney damage. Male C57BL/6J MASP-2 knockout (Masp2-/-) mice and wildtype (WT) mice were divided into a diabetic group and a non-diabetic group. Renal hypertrophy, albumin excretion, mesangial area and specific mRNA expressions in the renal cortex were measured after 8 and 12 weeks of diabetes. By two-way ANOVA it was tested if MASP-2 modulated the renal effects of diabetes, that is interaction. After 12 weeks of diabetes Masp2-/- diabetic mice had a smaller mesangium at 21.1% of the glomerular area (95% CI 19.7, 22.6) compared with WT diabetic mice, 25.2% (23.2, 27.2), p(interaction) = 0.001. After 8 weeks of diabetes, plasma cystatin C was 261.5 ng/mL (229.6, 297.8) in the WT diabetic group compared to 459.9 ng/mL (385.7, 548.3) in non-diabetic WT mice, p < 0.001. By contrast, no difference in plasma cystatin C levels was found between the Masp2-/- diabetic mice, 288.2 ng/mL (260.6, 318.6) and Masp2-/- non-diabetic mice, 293.5 ng/mL (221.0, 389.7), p = 0.86 and p(interaction) = 0.001. We demonstrated a protective effect of MASP-2 deficiency on mesangial hypertrophy after 12 weeks of diabetes and an effect on plasma cystatin C level. MASP-2 deficiency did, however, fail to protect against diabetic-induced alterations of kidney weight, albuminuria and renal mRNA expression of fibrotic- and oxidative stress markers.
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Affiliation(s)
- Holt Charlotte Brinck
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Halkjær Lene
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Dudler Tom
- Omeros Corporation, Seattle, Washington, USA
| | - Schwaeble Wilhelm
- Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, UK
| | | | - Thiel Steffen
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Østergaard Jakob Appel
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
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Denic A, Mullan AF, Alexander MP, Wilson LD, Augustine J, Luehrs AC, Stegall MD, Kline TL, Sharma V, Thompson RH, Rule AD. An Improved Method for Estimating Nephron Number and the Association of Resulting Nephron Number Estimates with Chronic Kidney Disease Outcomes. J Am Soc Nephrol 2023; 34:1264-1278. [PMID: 36958059 PMCID: PMC10356139 DOI: 10.1681/asn.0000000000000124] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 02/15/2023] [Indexed: 03/25/2023] Open
Abstract
SIGNIFICANCE STATEMENT Nephron number currently can be estimated only from glomerular density on a kidney biopsy combined with cortical volume from kidney imaging. Because of measurement biases, refinement of this approach and validation across different patient populations have been needed. The prognostic importance of nephron number also has been unclear. The authors present an improved method of estimating nephron number that corrects for several biases, resulting in a 27% higher nephron number estimate for donor kidneys compared with a prior method. After accounting for comorbidities, the new nephron number estimate does not differ between kidney donors and kidney patients with tumor and shows consistent associations with clinical characteristics across these two populations. The findings also indicate that low nephron number predicts CKD independent of biopsy and clinical characteristics in both populations. BACKGROUND Nephron number can be estimated from glomerular density and cortical volume. However, because of measurement biases, this approach needs refinement, comparison between disparate populations, and evaluation as a predictor of CKD outcomes. METHODS We studied 3020 living kidney donors and 1354 patients who underwent radical nephrectomy for tumor. We determined cortex volume of the retained kidney from presurgical imaging and glomerular density by morphometric analysis of needle core biopsy of the donated kidney and wedge sections of the removed kidney. Glomerular density was corrected for missing glomerular tufts, absence of the kidney capsule, and then tissue shrinkage on the basis of analysis of 30 autopsy kidneys. We used logistic regression (in donors) and Cox proportional hazard models (in patients with tumor) to assess the risk of CKD outcomes associated with nephron number. RESULTS Donors had 1.17 million nephrons per kidney; patients with tumor had 0.99 million nephrons per kidney. A lower nephron number was associated with older age, female sex, shorter height, hypertension, family history of ESKD, lower GFR, and proteinuria. After adjusting for these characteristics, nephron number did not differ between donors and patients with tumor. Low nephron number (defined by <5th or <10th percentile by age and sex in a healthy subset) in both populations predicted future risk of CKD outcomes independent of biopsy and clinical characteristics. CONCLUSIONS Compared with an older method for estimating nephron number, a new method that addresses several sources of bias results in nephron number estimates that are 27% higher in donors and 1% higher in patients with tumor and shows consistency between two populations. Low nephron number independently predicts CKD in both populations.
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Affiliation(s)
- Aleksandar Denic
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Aidan F Mullan
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota
| | - Mariam P Alexander
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Luke D Wilson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | | | - Anthony C Luehrs
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota
| | - Mark D Stegall
- Department of Surgery and Immunology, Mayo Clinic, Rochester, Minnesota
| | | | - Vidit Sharma
- Department of Urology, Mayo Clinic, Rochester, Minnesota
| | | | - Andrew D Rule
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
- Division of Epidemiology, Mayo Clinic, Rochester, Minnesota
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Okabayashi Y, Tsuboi N, Marumoto H, Sasaki T, Haruhara K, Kanzaki G, Koike K, Ueda H, Shimizu A, Puelles VG, D'Agati V, Yokoo T. Single-Nephron GFR in Different Glomerular Basement Membrane Stages of Membranous Nephropathy. KIDNEY360 2023; 4:e777-e786. [PMID: 37166967 PMCID: PMC10371379 DOI: 10.34067/kid.0000000000000142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 03/22/2023] [Indexed: 05/12/2023]
Abstract
Key Points The first study that estimated single-nephron GFR (SNGFR) in patients with membranous nephropathy (MN). Associations of SNGFR with MN staging by electron microscopy and clinicopathologic findings were cross-sectionally investigated. This study illustrates a role for disease-specific GBM structural lesions as determinants of SNGFR in patients with MN. Background Alterations in single-nephron dynamics have been demonstrated in animal models of membranous nephropathy (MN). This study applied a recently developed technique to estimate single-nephron parameters in human MN. Methods Single-nephron GFR (SNGFR) and single-nephron urinary protein excretion (SNUPE) were calculated by dividing total GFR and UPE by the total estimated number of nonglobally sclerotic glomeruli (NSG). The NSG number per kidney was estimated using cortical volume assessment and biopsy-based stereology. MN staging by electron microscopy was performed using Ehrenreich-Churg (EC) criteria. Single-nephron parameters were analyzed in relation to clinicopathological factors known to associate with disease outcomes. Results The study included 109 patients with MN (mean age 65 years; 73% male; eGFR 62 ml/min, 36% on renin-angiotensin-aldosterone system inhibitors prebiopsy). EC stages were I, 19%; II, 49%; III, 26%; and IV, 6%. There was no difference in glomerular volume among EC stage groups. With advancing EC stage, SNGFR and SNUPE decreased from mean 56–42 nl/min and 5.1–3.8 µ g/d, respectively. In multivariable models, EC stage was associated with SNGFR even after adjustment for key clinicopathological factors, such as reduced GFR, serum albumin, UPE, segmental glomerulosclerosis, chronic tubulointerstitial damage, and prebiopsy use of renin-angiotensin-aldosterone system inhibitors. By contrast, EC stage was not associated with glomerular volume and SNUPE after multivariable adjustment. Conclusions These results provide the first clinical evidence of alterations in single-nephron dynamics with advancing EC stage of human MN and support a role for disease-specific glomerular basement membrane structural lesions as determinants of SNGFR.
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Affiliation(s)
- Yusuke Okabayashi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Ill. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany
| | - Nobuo Tsuboi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Hirokazu Marumoto
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Takaya Sasaki
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kotaro Haruhara
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Go Kanzaki
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kentaro Koike
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Hiroyuki Ueda
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Akira Shimizu
- Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan
| | - Victor G. Puelles
- Ill. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany
| | - Vivette D'Agati
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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Denic A, Bogojevic M, Subramani R, Park WD, Smith BH, Alexander MP, Grande JP, Kukla A, Schinstock CA, Bentall AJ, Rule AD, Stegall MD. Changes in Glomerular Volume, Sclerosis, and Ischemia at 5 Years after Kidney Transplantation: Incidence and Correlation with Late Graft Failure. J Am Soc Nephrol 2023; 34:346-358. [PMID: 36396330 PMCID: PMC10103088 DOI: 10.1681/asn.2022040418] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 10/02/2022] [Indexed: 11/18/2022] Open
Abstract
SIGNIFICANCE STATEMENT Glomerular volume, ischemic glomeruli, and global glomerulosclerosis are not consistently assessed on kidney transplant biopsies. The authors evaluated morphometric measures of glomerular volume, the percentage of global glomerulosclerosis, and the percentage of ischemic glomeruli and assessed changes in these measures over time to determine whether such changes predict late allograft failure. All three features increased from transplant to five-year biopsy. Kidneys with smaller glomeruli at 5 years had more global glomerulosclerosis and a higher percentage of ischemic-appearing glomeruli. Smaller glomeruli and increasing percentages of global glomerulosclerosis and ischemic glomeruli at 5 years predicted allograft failure. Only increased percentage of ischemic glomeruli predicted allograft failure at 5 years independent of all Banff scores. Glomerular changes reflect pathologic processes that predicted allograft loss; measuring them quantitatively might enhance the current Banff system and provide biomarkers for intervention trials. BACKGROUND Histology can provide insight into the biology of renal allograft loss. However, studies are lacking that use quantitative morphometry to simultaneously assess changes in mean glomerular volume and in the percentages of globally sclerosed glomeruli (GSG) and ischemic-appearing glomeruli in surveillance biopsies over time to determine whether such changes are correlated with late graft failure. METHODS We used digital scans of surveillance biopsies (at implantation and at 1 and 5 years after transplantation) to morphometrically quantify glomerular volume and the percentages of GSG and ischemic-appearing glomeruli in a cohort of 835 kidney transplants. Cox proportional hazards models assessed the risk of allograft failure with these three glomerular features. RESULTS From implantation to 5 years, mean glomerular volume increased by nearly 30% (from 2.8×10 6 to 3.6×10 6 µm 3 ), mean percentage of GSG increased from 3.2% to 13.2%, and mean percentage of ischemic-appearing glomeruli increased from 0.8% to 9.5%. Higher percentages of GSG and ischemic-appearing glomeruli at 5-year biopsy predicted allograft loss. The three glomerular features at 5-year biopsy were related; the percentage of GSG and the percentage of ischemic glomeruli were positively correlated, and both were inversely correlated to glomerular volume. At 5 years, only 5.3% of biopsies had ≥40% ischemic glomeruli, but 45% of these grafts failed (versus 11.6% for <40% ischemic glomeruli). Higher Banff scores were more common with increasing percentages of GSG and ischemia, but at 5 years, only the percentage of ischemic glomeruli added to predictive models adjusted for Banff scores. CONCLUSIONS Glomerular changes reflect important pathologic processes that predict graft loss. Measuring glomerular changes quantitatively on surveillance biopsies, especially the proportion of ischemic-appearing glomeruli, may enhance the current Banff system and be a useful surrogate end point for clinical intervention trials. PODCAST This article contains a podcast at.
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Affiliation(s)
- Aleksandar Denic
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Marija Bogojevic
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Rashmi Subramani
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Walter D. Park
- Department of Surgery and Immunology, Mayo Clinic, Rochester, Minnesota
| | - Byron H. Smith
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Mariam P. Alexander
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Joseph P. Grande
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Aleksandra Kukla
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | | | - Andrew J. Bentall
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Andrew D. Rule
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Mark D. Stegall
- Department of Surgery and Immunology, Mayo Clinic, Rochester, Minnesota
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Oba R, Kanzaki G, Haruhara K, Sasaki T, Okabayashi Y, Koike K, Tsuboi N, Yokoo T. Non-dipping pulse rate and chronic changes of the kidney in patients with chronic kidney disease. Front Cardiovasc Med 2023; 10:911773. [PMID: 36891248 PMCID: PMC9986326 DOI: 10.3389/fcvm.2023.911773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 01/30/2023] [Indexed: 02/22/2023] Open
Abstract
Introduction An insufficient decrease in nocturnal pulse rate (PR), non-dipping PR, reflects autonomic imbalance and is associated with cardiovascular events and all-cause mortality. We aimed to investigate the clinical and microanatomical structural findings associated with the non-dipping PR status in patients with chronic kidney disease (CKD). Methods This cross-sectional study included 135 patients who underwent ambulatory blood pressure monitoring and kidney biopsy concurrently at our institution between 2016 and 2019. Non-dipping PR status was defined as (daytime PR-nighttime PR)/daytime PR <0.1. We compared clinical parameters and microstructural changes in the kidney between patients with and without non-dipping PR, including 24 h proteinuria, glomerular volume, and Mayo Clinic/Renal Pathology Society Chronicity Score. Results The median age was 51 years (interquartile range: 35-63), 54% of which were male, and the median estimated glomerular filtration rate was 53.0 (30.0-75.0) mL/min/1.73 m2. Non-dipping PR status was observed in 39 patients. Patients with non-dipping PR were older and had worse kidney function, higher blood pressure, greater prevalence of dyslipidemia, lower hemoglobin levels, and a larger amount of urinary protein excretion than patients with dipping PR. Patients with non-dipping PR had more severe glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriosclerosis. In the multivariable analysis, the severe chronic changes of the kidney were associated with non-dipping PR status after adjusting for age, sex, and other clinical parameters (odds ratio = 20.8; 95% confidence interval, 2.82-153; P = 0.003). Conclusion This study is the first to indicate that non-dipping PR is significantly associated with chronic microanatomical changes in the kidneys of patients with CKD.
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Affiliation(s)
- Rina Oba
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Go Kanzaki
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kotaro Haruhara
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Takaya Sasaki
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Yusuke Okabayashi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kentaro Koike
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Nobuo Tsuboi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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Basso MN, Barua M, John R, Khademi A. Explainable Biomarkers for Automated Glomerular and Patient-Level Disease Classification. KIDNEY360 2021; 3:534-545. [PMID: 35582169 PMCID: PMC9034815 DOI: 10.34067/kid.0005102021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 12/08/2021] [Indexed: 01/12/2023]
Abstract
Pathologists use multiple microscopy modalities to assess renal biopsy specimens. Besides usual diagnostic features, some changes are too subtle to be properly defined. Computational approaches have the potential to systematically quantitate subvisual clues, provide pathogenetic insight, and link to clinical outcomes. To this end, a proof-of-principle study is presented demonstrating that explainable biomarkers through machine learning can distinguish between glomerular disorders at the light-microscopy level. The proposed system used image analysis techniques and extracted 233 explainable biomarkers related to color, morphology, and microstructural texture. Traditional machine learning was then used to classify minimal change disease (MCD), membranous nephropathy (MN), and thin basement membrane nephropathy (TBMN) diseases on a glomerular and patient-level basis. The final model combined the Gini feature importance set and linear discriminant analysis classifier. Six morphologic (nuclei-to-glomerular tuft area, nuclei-to-glomerular area, glomerular tuft thickness greater than ten, glomerular tuft thickness greater than three, total glomerular tuft thickness, and glomerular circularity) and four microstructural texture features (luminal contrast using wavelets, nuclei energy using wavelets, nuclei variance using color vector LBP, and glomerular correlation using GLCM) were, together, the best performing biomarkers. Accuracies of 77% and 87% were obtained for glomerular and patient-level classification, respectively. Computational methods, using explainable glomerular biomarkers, have diagnostic value and are compatible with our existing knowledge of disease pathogenesis. Furthermore, this algorithm can be applied to clinical datasets for novel prognostic and mechanistic biomarker discovery.
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Affiliation(s)
- Matthew Nicholas Basso
- Image Analysis in Medicine Lab (IAMLAB), Department of Electrical, Computer, and Biomedical Engineering, Ryerson University, Toronto, Canada
| | - Moumita Barua
- Division of Nephrology, University Health Network, Toronto, Canada,Toronto General Hospital Research Institute, Toronto General Hospital, Toronto, Canada,Department of Medicine, University of Toronto, Toronto, Canada,Institute of Medical Sciences, University of Toronto, Toronto, Canada
| | - Rohan John
- Department of Pathology, University Health Network, Toronto, Canada
| | - April Khademi
- Image Analysis in Medicine Lab (IAMLAB), Department of Electrical, Computer, and Biomedical Engineering, Ryerson University, Toronto, Canada,Keenan Research Center for Biomedical Science, St. Michael’s Hospital, Unity Health Network, Toronto, Canada,Institute for Biomedical Engineering, Science, and Technology (iBEST), a partnership between St. Michael’s Hospital and Ryerson University, Toronto, Canada
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Torigoe K, Muta K, Tsuji K, Yamashita A, Abe S, Ota Y, Mukae H, Nishino T. Safety of Renal Biopsy by Physicians with Short Nephrology Experience. Healthcare (Basel) 2021; 9:healthcare9040474. [PMID: 33923650 PMCID: PMC8072574 DOI: 10.3390/healthcare9040474] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 04/13/2021] [Accepted: 04/15/2021] [Indexed: 12/18/2022] Open
Abstract
Percutaneous renal biopsy is an essential tool for diagnosing various renal diseases; however, little is known about whether renal biopsy performed by physicians with short nephrology experience is safe in Japan. This study included 238 patients who underwent percutaneous renal biopsy between April 2017 and September 2020. We retrospectively analyzed the frequency of post-renal biopsy complications (hemoglobin decrease of ≥10%, hypotension, blood transfusion, renal artery embolization, nephrectomy and death) and compared their incidence among physicians with varied experience in nephrology. After renal biopsy, a hemoglobin decrease of ≥10%, hypotension and transfusion occurred in 13.1%, 3.8% and 0.8% of patients, respectively. There were no cases of post-biopsy renal artery embolism, nephrectomy, or death. The composite complication rate was 16.0%. The incidence of post-biopsy complications was similar between physicians with ≥3 years and <3 years of clinical nephrology experience (12.5% vs. 16.8%, p = 0.64). Furthermore, the post-biopsy composite complication rates were similar between physicians with ≥6 months and <6 months of clinical nephrology experience (16.3% vs. 15.6%, p > 0.99). Under attending nephrologist supervision, a physician with short clinical nephrology experience can safely perform renal biopsy.
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Affiliation(s)
- Kenta Torigoe
- Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan; (K.T.); (K.T.); (A.Y.); (S.A.); (Y.O.); (T.N.)
| | - Kumiko Muta
- Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan; (K.T.); (K.T.); (A.Y.); (S.A.); (Y.O.); (T.N.)
- Correspondence: ; Tel.: +81-95-819-7282
| | - Kiyokazu Tsuji
- Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan; (K.T.); (K.T.); (A.Y.); (S.A.); (Y.O.); (T.N.)
| | - Ayuko Yamashita
- Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan; (K.T.); (K.T.); (A.Y.); (S.A.); (Y.O.); (T.N.)
| | - Shinichi Abe
- Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan; (K.T.); (K.T.); (A.Y.); (S.A.); (Y.O.); (T.N.)
| | - Yuki Ota
- Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan; (K.T.); (K.T.); (A.Y.); (S.A.); (Y.O.); (T.N.)
| | - Hiroshi Mukae
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan;
| | - Tomoya Nishino
- Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan; (K.T.); (K.T.); (A.Y.); (S.A.); (Y.O.); (T.N.)
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Sheth RA, Baerlocher MO, Connolly BL, Dariushnia SR, Shyn PB, Vatsky S, Tam AL, Gupta S. Society of Interventional Radiology Quality Improvement Standards on Percutaneous Needle Biopsy in Adult and Pediatric Patients. J Vasc Interv Radiol 2020; 31:1840-1848. [DOI: 10.1016/j.jvir.2020.07.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 07/10/2020] [Indexed: 12/13/2022] Open
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Haruhara K, Tsuboi N, Sasaki T, Amano H, Tanaka M, Koike K, Kanzaki G, Okabayashi Y, Miyazaki Y, Ogura M, Yokoo T. Volume Ratio of Glomerular Tufts to Bowman Capsules and Renal Outcomes in Nephrosclerosis. Am J Hypertens 2019; 32:45-53. [PMID: 30358804 DOI: 10.1093/ajh/hpy147] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Accepted: 10/16/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The concomitant appearance of glomerular collapse and enlargement is characteristic of the histological findings in nephrosclerosis. However, no previous study quantitatively examined the clinicopathological significance of this feature in patients with biopsy-proven nephrosclerosis. METHODS Renal biopsy specimens and follow-up data from nephrosclerosis patients with estimated glomerular filtration rates >30 ml/min/1.73 m2 at diagnosis were retrospectively reviewed. Mean volumes for glomerular tufts (GV) and Bowman capsules (BV) were separately calculated, based on the measurement of all areas of glomerular tufts and Bowman capsules in a cross-section of biopsy specimens. The G/B ratio was defined as the ratio of GV to BV. The doubling of serum creatinine levels (DSC) and the initiation of renal replacement therapies (end-stage renal disease (ESRD)) were examined as renal outcome indices. RESULTS A total of 67 patients with biopsy-proven nephrosclerosis were included. Clinicopathological findings at biopsy, other than GV, were comparable among all patients, irrespective of G/B ratio. Overall, 25 patients (37%) developed DSC and 9 (13%) developed ESRD during the median observation periods of 7.8 and 8.5 years, respectively. Renal survival curve analyses indicated a significantly worse prognosis for patients with a low G/B ratio, as compared with those with a high G/B ratio. Cox hazard analyses for DSC identified low G/B ratio as a significant predictor, but not low GV or BV. CONCLUSIONS These results suggest that the quantitative evaluation of G/B ratio may detect subtle abnormalities in the glomerulus, indicating the subsequent renal outcomes of nephrosclerosis patients.
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Affiliation(s)
- Kotaro Haruhara
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Nobuo Tsuboi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Takaya Sasaki
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Hoichi Amano
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Mai Tanaka
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kentaro Koike
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Go Kanzaki
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Yusuke Okabayashi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Yoichi Miyazaki
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Makoto Ogura
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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Antunes PRB, Prado FFM, de Souza FTA, de Siqueira EC, de Campos MÁ, Álvares MCB, Neto RB. Clinical complications in renal biopsy using two different needle gauges: The impact of large hematomas, a random clinical trial study. Int J Urol 2018; 25:544-548. [PMID: 29687478 DOI: 10.1111/iju.13559] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Accepted: 02/20/2018] [Indexed: 11/28/2022]
Abstract
OBJECTIVE To compare complications of ultrasound-guided percutaneous renal biopsy using two needle gauges (16-G and 18-G). METHODS A total of 238 individuals with renal biopsy indication were included and randomly separated into two groups: ultrasound-guided percutaneous renal biopsy procedure carried out with a 16-G or 18-G needle. The adequacy of biopsy samples and post-procedure complications were compared between the two groups. RESULTS The procedures carried out with a 16-G needle collected fragments with a mean of 22.1 ± 10.8 glomeruli, and those carried out with an 18-G needle had a mean of 17.5 ± 9.4 glomeruli. Patients submitted to renal biopsies with a 16-G needle had a higher likelihood of having a complication (OR5.1, 95% CI 1.7-15.4, P = 0.001). The overall mean volume of post-biopsy hematoma in patients with complications was significantly larger than those without complications (44 ± 56.1 mL vs 5.9 ± 6.6 mL; P < 0.001). CONCLUSIONS Renal biopsies carried out by ultrasonography using an 18-G needle provide adequate histological analysis, showing a lower amount of glomeruli but with similar clinical quality as a 16-G needle. Furthermore, it is associated with a lower risk of procedure-related complications.
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Affiliation(s)
- Paulo Ramos Botelho Antunes
- Research Group on Diagnostic and Therapeutic Radiology, Santa Casa Hospital, Belo Horizonte, Minas Gerais, Brazil.,Institute of Education and Research of Santa Casa de Belo Horizonte, Santa Casa Hospital, Belo Horizonte, Minas Gerais, Brazil
| | | | | | - Elisa Carvalho de Siqueira
- Research Group on Diagnostic and Therapeutic Radiology, Santa Casa Hospital, Belo Horizonte, Minas Gerais, Brazil
| | - Marcos Álvares de Campos
- Research Group on Diagnostic and Therapeutic Radiology, Santa Casa Hospital, Belo Horizonte, Minas Gerais, Brazil.,Institute of Education and Research of Santa Casa de Belo Horizonte, Santa Casa Hospital, Belo Horizonte, Minas Gerais, Brazil
| | | | - Rene Berindoague Neto
- Institute of Education and Research of Santa Casa de Belo Horizonte, Santa Casa Hospital, Belo Horizonte, Minas Gerais, Brazil
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11
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Sasaki T, Tsuboi N, Haruhara K, Okabayashi Y, Kanzaki G, Koike K, Kobayashi A, Yamamoto I, Ogura M, Yokoo T. Bowman Capsule Volume and Related Factors in Adults With Normal Renal Function. Kidney Int Rep 2017; 3:314-320. [PMID: 29725634 PMCID: PMC5932303 DOI: 10.1016/j.ekir.2017.10.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 10/07/2017] [Accepted: 10/16/2017] [Indexed: 01/22/2023] Open
Abstract
Introduction Alterations in glomerular filtration can considerably influence the dynamics and functions of the Bowman capsule. Despite the potentially important role in maintaining normal renal functions, few studies have focused on Bowman capsule volume in normal human kidneys. Methods We analyzed specimens from biopsies performed 1 hour after kidney transplantation from living donors without apparent renal disease. The measurements of all cross-sectional areas of the Bowman capsules and glomerular capillaries were used to estimate the mean Bowman capsule volume (BV) and glomerular capillary volume (GV) in each subject. The G/B ratio was defined as the ratio of GV to BV. The morphometric findings were examined in relation to the clinical findings in donors just before kidney transplantation. Results We analyzed 37 adults with a mean creatinine clearance of 111 ml/min. The mean BV and GV of these subjects were 6.10 ± 2.46 × 106 μm3 and 3.83 ± 1.52 × 106 μm3, respectively. Both the BV and GV varied up to 6-fold and were significantly higher in elderly, obese, or hypertensive subjects in comparison to nonelderly, nonobese, or normotensive subjects, whereas the renal function of each subgroup was similar. The G/B ratio (0.63 ± 0.05) was unaffected, and BV and GV were strongly correlated regardless of these clinical factors (r = 0.980 [95% confidence interval = 0.961−0.990], P < 0.001). Conclusion In the normal adult kidney, there may be an optimal BV to GV ratio for maintaining effective filtration in a variety of clinical situations, including advanced age, obesity, and hypertension.
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Affiliation(s)
- Takaya Sasaki
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Nobuo Tsuboi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Correspondence: Nobuo Tsuboi, Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo, Japan.
| | - Kotaro Haruhara
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Yusuke Okabayashi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Go Kanzaki
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kentaro Koike
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Akimitsu Kobayashi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Izumi Yamamoto
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Makoto Ogura
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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12
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Xu DM, Chen M, Zhou FD, Zhao MH. Risk Factors for Severe Bleeding Complications in Percutaneous Renal Biopsy. Am J Med Sci 2017; 353:230-235. [DOI: 10.1016/j.amjms.2016.12.019] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Revised: 12/25/2016] [Accepted: 12/29/2016] [Indexed: 01/19/2023]
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13
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Denic A, Lieske JC, Chakkera HA, Poggio ED, Alexander MP, Singh P, Kremers WK, Lerman LO, Rule AD. The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging. J Am Soc Nephrol 2016; 28:313-320. [PMID: 27401688 DOI: 10.1681/asn.2016020154] [Citation(s) in RCA: 265] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Accepted: 05/18/2016] [Indexed: 01/28/2023] Open
Abstract
Nephron number may be an important determinant of kidney health but has been difficult to study in living humans. We evaluated 1638 living kidney donors at Mayo Clinic (MN and AZ sites) and Cleveland Clinic. We obtained cortical volumes of both kidneys from predonation computed tomography scans. At the time of kidney transplant, we obtained and analyzed the sections of a biopsy specimen of the cortex to determine the density of both nonsclerotic and globally sclerotic glomeruli; the total number of glomeruli was estimated from cortical volume×glomerular density. Donors 18-29 years old had a mean 990,661 nonsclerotic glomeruli and 16,614 globally sclerotic glomeruli per kidney, which progressively decreased to 520,410 nonsclerotic glomeruli per kidney and increased to 141,714 globally sclerotic glomeruli per kidney in donors 70-75 years old. Between the youngest and oldest age groups, the number of nonsclerotic glomeruli decreased by 48%, whereas cortical volume decreased by only 16% and the proportion of globally sclerotic glomeruli on biopsy increased by only 15%. Clinical characteristics that independently associated with fewer nonsclerotic glomeruli were older age, shorter height, family history of ESRD, higher serum uric acid level, and lower measured GFR. The incomplete representation of nephron loss with aging by either increased glomerulosclerosis or by cortical volume decline is consistent with atrophy and reabsorption of globally sclerotic glomeruli and hypertrophy of remaining nephrons. In conclusion, lower nephron number in healthy adults associates with characteristics reflective of both lower nephron endowment at birth and subsequent loss of nephrons.
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Affiliation(s)
| | | | - Harini A Chakkera
- Division of Nephrology and Hypertension, Mayo Clinic, Scottsdale, Arizona; and
| | | | | | | | - Walter K Kremers
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
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14
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Denic A, Lieske JC, Chakkera HA, Poggio ED, Alexander MP, Singh P, Kremers WK, Lerman LO, Rule AD. The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging. J Am Soc Nephrol 2016. [PMID: 27401688 DOI: 10.1681/asn.201602154] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Nephron number may be an important determinant of kidney health but has been difficult to study in living humans. We evaluated 1638 living kidney donors at Mayo Clinic (MN and AZ sites) and Cleveland Clinic. We obtained cortical volumes of both kidneys from predonation computed tomography scans. At the time of kidney transplant, we obtained and analyzed the sections of a biopsy specimen of the cortex to determine the density of both nonsclerotic and globally sclerotic glomeruli; the total number of glomeruli was estimated from cortical volume×glomerular density. Donors 18-29 years old had a mean 990,661 nonsclerotic glomeruli and 16,614 globally sclerotic glomeruli per kidney, which progressively decreased to 520,410 nonsclerotic glomeruli per kidney and increased to 141,714 globally sclerotic glomeruli per kidney in donors 70-75 years old. Between the youngest and oldest age groups, the number of nonsclerotic glomeruli decreased by 48%, whereas cortical volume decreased by only 16% and the proportion of globally sclerotic glomeruli on biopsy increased by only 15%. Clinical characteristics that independently associated with fewer nonsclerotic glomeruli were older age, shorter height, family history of ESRD, higher serum uric acid level, and lower measured GFR. The incomplete representation of nephron loss with aging by either increased glomerulosclerosis or by cortical volume decline is consistent with atrophy and reabsorption of globally sclerotic glomeruli and hypertrophy of remaining nephrons. In conclusion, lower nephron number in healthy adults associates with characteristics reflective of both lower nephron endowment at birth and subsequent loss of nephrons.
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Affiliation(s)
| | | | - Harini A Chakkera
- Division of Nephrology and Hypertension, Mayo Clinic, Scottsdale, Arizona; and
| | | | | | | | - Walter K Kremers
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
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15
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Visconti L, Cernaro V, Ricciardi CA, Lacava V, Pellicanò V, Lacquaniti A, Buemi M, Santoro D. Renal biopsy: Still a landmark for the nephrologist. World J Nephrol 2016; 5:321-327. [PMID: 27458561 PMCID: PMC4936339 DOI: 10.5527/wjn.v5.i4.321] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2016] [Revised: 03/14/2016] [Accepted: 04/06/2016] [Indexed: 02/06/2023] Open
Abstract
Renal biopsy was performed for the first time more than one century ago, but its clinical use was routinely introduced in the 1950s. It is still an essential tool for diagnosis and choice of treatment of several primary or secondary kidney diseases. Moreover, it may help to know the expected time of end stage renal disease. The indications are represented by nephritic and/or nephrotic syndrome and rapidly progressive acute renal failure of unknown origin. Nowadays, it is performed mainly by nephrologists and radiologists using a 14-18 gauges needle with automated spring-loaded biopsy device, under real-time ultrasound guidance. Bleeding is the major primary complication that in rare cases may lead to retroperitoneal haemorrhage and need for surgical intervention and/or death. For this reason, careful evaluation of risks and benefits must be taken into account, and all procedures to minimize the risk of complications must be observed. After biopsy, an observation time of 12-24 h is necessary, whilst a prolonged observation may be needed rarely. In some cases it could be safer to use different techniques to reduce the risk of complications, such as laparoscopic or transjugular renal biopsy in patients with coagulopathy or alternative approaches in obese patients. Despite progress in medicine over the years with the introduction of more advanced molecular biology techniques, renal biopsy is still an irreplaceable tool for nephrologists.
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16
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Understanding the role of maternal diet on kidney development; an opportunity to improve cardiovascular and renal health for future generations. Nutrients 2015; 7:1881-905. [PMID: 25774605 PMCID: PMC4377888 DOI: 10.3390/nu7031881] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2014] [Revised: 03/02/2015] [Accepted: 03/03/2015] [Indexed: 01/08/2023] Open
Abstract
The leading causes of mortality and morbidity worldwide are cardiovascular disease (high blood pressure, high cholesterol and renal disease), cancer and diabetes. It is increasingly obvious that the development of these diseases encompasses complex interactions between adult lifestyle and genetic predisposition. Maternal malnutrition can influence the fetal and early life environment and pose a risk factor for the future development of adult diseases, most likely due to impaired organogenesis in the developing offspring. This then predisposes these offspring to cardiovascular disease and renal dysfunction in adulthood. Studies in experimental animals have further illustrated the significant impact maternal diet has on offspring health. Many studies report changes in kidney structure (a reduction in the number of nephrons in the kidney) in offspring of protein-deprived dams. Although the early studies suggested that increased blood pressure was also present in offspring of protein-restricted dams, this is not a universal finding and requires clarification. Importantly, to date, the literature offers little to no understanding of when in development these changes in kidney development occur, nor are the cellular and molecular mechanisms that drive these changes well characterised. Moreover, the mechanisms linking maternal nutrition and a suboptimal renal phenotype in offspring are yet to be discerned—one potential mechanism involves epigenetics. This review will focus on recent information on potential mechanisms by which maternal nutrition (focusing on malnutrition due to protein restriction, micronutrient restriction and excessive fat intake) influences kidney development and thereby function in later life.
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17
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Crobe A, Desogus M, Sanna A, Fraschini M, Gerosa C, Fanni D, Fanos V, Van Eyken P, Faa G. Decreasing podocyte number during human kidney intrauterine development. Am J Physiol Renal Physiol 2014; 307:F1033-40. [DOI: 10.1152/ajprenal.00165.2014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Nephron number at birth has relevant clinical importance with implications for long-term renal health. In recent years, the podocyte depletion hypothesis has emerged as an important concept in kidney pathology. This study was aimed at verifying whether human podocyte number changes significantly during intrauterine life. To this end, 62 subjects with gestational ages ranging from 20 to 41 wk were examined. Kidney sections were stained with hematoxylin and eosin and digitally scanned at ×400 magnification. Subjects were subdivided into fetuses (gestational age ≤24 wk, n = 5), preterms (gestational age ≥25 and ≤36 wk, n = 39), and full-term newborns (gestational age ≥37 wk, n = 18). The average podocyte number of 1,908 ± 645, 1,394 ± 498, and 1,126 ± 256 was, respectively, observed in fetuses, preterms, and full-term newborns. A significant main effect ( P = 0.0051) of gestational age on podocyte number was observed with a significantly lower number in full-term newborns than in fetuses ( P < 0.01). Intragroup variability was also observed. We speculate that variations in podocyte number could be correlated with factors such as drugs and maternal diet occurring during intrauterine life. In conclusion, this study shows, for the first time, a decreasing trend in podocyte number during gestation.
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Affiliation(s)
- A. Crobe
- Section of Pathology, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
| | - M. Desogus
- Section of Pathology, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
| | - A. Sanna
- Section of Pathology, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
| | - M. Fraschini
- Department of Electrical and Electronics Engineering, University of Cagliari, Cagliari, Italy
| | - C. Gerosa
- Section of Pathology, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
| | - D. Fanni
- Section of Pathology, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
| | - V. Fanos
- NICU, Neonatal Pathology, Puericulture Institute and Neonatal Section, University of Cagliari, Cagliari, Italy; and
| | - P. Van Eyken
- Department of Pathology, KU Leuven, Leuven, Belgium
| | - G. Faa
- Section of Pathology, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
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18
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Plagov A, Lan X, Rai P, Kumar D, Lederman R, Rehman S, Malhotra A, Ding G, Chander PN, Singhal PC. Modulation of renin angiotensin system predominantly alters sclerotic phenotype of glomeruli in HIVAN. Histol Histopathol 2014; 29:1575-81. [PMID: 24892944 DOI: 10.14670/hh-29.1575] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
HIV-associated nephropathy (HIVAN) is a common complication of HIV-1 infection in patients with African ancestry in general and with APOL1 gene risk variants in particular. Although collapsing glomerulopathy is considered a hallmark of HIVAN, significant numbers of glomeruli in patients with HIVAN also display other variants of focal segmental glomerulosclerosis (FSGS). We propose that collapsed glomeruli as well as glomeruli with other variants of FSGS are manifestations of HIVAN and their prevalence depends on associated host factors. We explored the role of the renin-angiotensin system (RAS) in the manifestation of any specific glomerular phenotype in HIVAN. To evaluate the role of the RAS we have used a genetically engineered mouse model of HIVAN (Tg26) with two and four copies of angiotensinogen (Agt) gene (Tg26/Agt2 and Tg26/Agt4). In Tg26/Agt2, 1 out of 6 glomeruli exhibited sclerosed phenotype, whereas 1 out of 25 glomeruli displayed collapsed phenotype; on the other hand, in Tg26/Agt4, 1 out of 3 glomeruli exhibited sclerotic phenotype and only 1 out of 7 glomeruli showed collapsed phenotype. To inhibit the effect of RAS, Tg26/Agt2 were administered captopril, aliskiren, aliskiren plus captopril or aliskiren plus telmisartan by miniosmotic pumps for 4 weeks. In all experimental groups there was a significant reduction in percentage of sclerosed glomeruli and only minimal reduction in collapsed glomeruli compared to normal saline receiving Tg26/Agt2. These findings suggest that the manifestation of the sclerosed phenotype in HIVAN is predominantly dependent on activation of the RAS.
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Affiliation(s)
- Andrei Plagov
- Renal Molecular Research Laboratory, Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Xiqian Lan
- Renal Molecular Research Laboratory, Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Partab Rai
- Renal Molecular Research Laboratory, Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Dileep Kumar
- Renal Molecular Research Laboratory, Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Rivka Lederman
- Renal Molecular Research Laboratory, Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Shabina Rehman
- Renal Molecular Research Laboratory, Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Ashwani Malhotra
- Renal Molecular Research Laboratory, Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Guohua Ding
- Renal Molecular Research Laboratory, Feinstein Institute for Medical Research, Manhasset, NY, USA
| | - Praveen N Chander
- Department of Pathology, New York Medical College, Valhalla, NY, USA
| | - Pravin C Singhal
- Renal Molecular Research Laboratory, Feinstein Institute for Medical Research, Manhasset, NY, USA.
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Hoy WE, Samuel T, Mott SA, Kincaid-Smith PS, Fogo AB, Dowling JP, Hughson MD, Sinniah R, Pugsley DJ, Kirubakaran MG, Douglas-Denton RN, Bertram JF. Renal biopsy findings among Indigenous Australians: a nationwide review. Kidney Int 2012; 82:1321-31. [PMID: 22932120 DOI: 10.1038/ki.2012.307] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Australia's Indigenous people have high rates of chronic kidney disease and kidney failure. To define renal disease among these people, we reviewed 643 renal biopsies on Indigenous people across Australia, and compared them with 249 biopsies of non-Indigenous patients. The intent was to reach a consensus on pathological findings and terminology, quantify glomerular size, and establish and compare regional biopsy profiles. The relative population-adjusted biopsy frequencies were 16.9, 6.6, and 1, respectively, for Aboriginal people living remotely/very remotely, for Torres Strait Islander people, and for non-remote-living Aboriginal people. Indigenous people more often had heavy proteinuria and renal failure at biopsy. No single condition defined the Indigenous biopsies and, where biopsy rates were high, all common conditions were in absolute excess. Indigenous people were more often diabetic than non-Indigenous people, but diabetic changes were still present in fewer than half their biopsies. Their biopsies also had higher rates of segmental sclerosis, post-infectious glomerulonephritis, and mixed morphologies. Among the great excess of biopsies in remote/very remote Aborigines, females predominated, with younger age at biopsy and larger mean glomerular volumes. Glomerulomegaly characterized biopsies with mesangiopathic changes only, with IgA deposition, or with diabetic change, and with focal segmental glomerulosclerosis (FSGS). This review reveals great variations in biopsy rates and findings among Indigenous Australians, and findings refute the prevailing dogma that most indigenous renal disease is due to diabetes. Glomerulomegaly in remote/very remote Aboriginal people is probably due to nephron deficiency, in part related to low birth weight, and probably contributes to the increased susceptibility to kidney disease and the predisposition to FSGS.
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Affiliation(s)
- Wendy E Hoy
- Centre for Chronic Disease, School of Medicine, The University of Queensland, Herston, Queensland, Australia.
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Weil EJ, Lemley KV, Mason CC, Yee B, Jones LI, Blouch K, Lovato T, Richardson M, Myers BD, Nelson RG. Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy. Kidney Int 2012; 82:1010-7. [PMID: 22718189 PMCID: PMC3472108 DOI: 10.1038/ki.2012.234] [Citation(s) in RCA: 216] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Podocyte detachment and reduced endothelial cell fenestration and relationships between these features and the classic structural changes of diabetic nephropathy have not been described in patients with type 2 diabetes. Here we studied these relationships in 37 Pima Indians with type 2 diabetes of whom 11 had normal albuminuria, 16 had microalbuminuria, and 10 had macroalbuminuria. Biopsies from 10 kidney donors (not American Indians) showed almost undetectable (0.03%) podocyte detachment and 43.5% endothelial cell fenestration. In patients with type 2 diabetes, by comparison, the mean percentage of podocyte detachment was significantly higher in macroalbuminuria (1.48%) than in normal albuminuria (0.41%) or microalbuminuria (0.37%). Podocyte detachment correlated significantly with podocyte number per glomerulus and albuminuria. The mean percentage of endothelial cell fenestration was significantly lower in macroalbuminuria (19.3%) than in normal albuminuria (27.4%) or microalbuminuria (27.2%) and correlated significantly with glomerular basement membrane thickness, albuminuria, fractional mesangial area, and the glomerular filtration rate (iothalamate clearance). Podocyte detachment and diminished endothelial cell fenestration were not correlated, but were related to classic lesions of diabetic nephropathy. Thus, our findings confirm the important role these injuries play in the development and progression of kidney disease in type 2 diabetes, just as they do in type 1 diabetes. Whether podocyte detachment creates conduits for proteins to escape the glomerular circulation and reduced endothelial fenestration lowers glomerular hydraulic permeability requires further study.
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Affiliation(s)
- E Jennifer Weil
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85014-4972, USA.
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21
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Bataille S, Jourde N, Daniel L, Mondain JR, Faure M, Gobert P, Alcheikh-Hassan Z, Lankester M, Giaime P, Gaudart J, Dussol B, Berland Y, Burtey S. Comparative safety and efficiency of five percutaneous kidney biopsy approaches of native kidneys: a multicenter study. Am J Nephrol 2012; 35:387-93. [PMID: 22508466 DOI: 10.1159/000337932] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Accepted: 03/03/2012] [Indexed: 11/19/2022]
Abstract
BACKGROUND Renal biopsy (RB) is necessary for the diagnosis, prognosis, and therapy guidance of native kidney diseases. Few studies have compared outcomes of RB procedures. We retrospectively compared the safety and efficiency of five biopsy procedures. METHODS The number of glomeruli on light microscopy (LM) and on immunofluorescence (IF) and serious adverse events following RB performed in five nephrology units (C1-C5) were collected. C1 performed ultrasound (US) assessment before RB and used a 14-gauge core-cutting needle biopsy gun, C2 US guidance and a 14-gauge needle, C3 tomodensitometry guidance and a 14-gauge needle, C4 US guidance and a 16-gauge needle, and C5 tomodensitometry guidance and a 16-gauge needle. RESULTS RB was performed in 943 adults between January 2006 and July 2010. Serious adverse events occurred in 1.5% of biopsies. The complication rate was not different between nephrology units. The mean number of glomeruli on biopsy was 14.2 ± 8.6 with LM and 4.4 ± 3.3 on IF. It was different according to the nephrology unit for LM (p = 0.01) and for IF (p < 0.001). The number of failed biopsies was influenced by the nephrology unit and radiological guidance technique, favoring real-time US guidance. Failed biopsies using US or tomodensitometry assessment before RB was certainly due to kidney imprecise localization since it was often non-renal tissue sampling. At least 10 glomeruli were found in 69% of biopsies on LM. This rate varied according to the nephrology unit (p = 0.004) and was higher when 14-gauge needles were used in comparison with 16-gauge needles. CONCLUSION RB is safe regardless of the technical procedure, but radiological guidance and needle size influence the efficiency of biopsies.
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Affiliation(s)
- Stanislas Bataille
- Centre de néphrologie et transplantation, AP-HM, Hôpital de la Conception, Marseille, France
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Cullen-McEwen LA, Armitage JA, Nyengaard JR, Moritz KM, Bertram JF. A design-based method for estimating glomerular number in the developing kidney. Am J Physiol Renal Physiol 2011; 300:F1448-53. [PMID: 21411478 DOI: 10.1152/ajprenal.00055.2011] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Low glomerular (nephron) endowment has been associated with an increased risk of cardiovascular and renal disease in adulthood. Nephron endowment in humans is determined by 36 wk of gestation, while in rats and mice nephrogenesis ends several days after birth. Specific genes and environmental perturbations have been shown to regulate nephron endowment. Until now, design-based method for estimating nephron number in developing kidneys was unavailable. This was due in part to the difficulty associated with unambiguously identifying developing glomeruli in histological sections. Here, we describe a method that uses lectin histochemistry to identify developing glomeruli and the physical disector/fractionator principle to provide unbiased estimates of total glomerular number (N(glom)). We have characterized N(glom) throughout development in kidneys from 76 rats and model this development with a 5-parameter logistic equation to predict N(glom) from embryonic day 17.25 to adulthood (r(2) = 0.98). This approach represents the first design-based method with which to estimate N(glom) in the developing kidney.
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Affiliation(s)
- Luise A Cullen-McEwen
- Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Victoria, Australia
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Abstract
Development of the kidney can be altered in utero in response to a suboptimal environment. The intrarenal factors that have been most well characterized as being sensitive to programming events are kidney mass/nephron endowment, the renin-angiotensin system, tubular sodium handling, and the renal sympathetic nerves. Newborns that have been subjected to an adverse intrauterine environment may thus begin life at a distinct disadvantage, in terms of renal function, at a time when the kidney must take over the primary role for extracellular fluid homeostasis from the placenta. A poor beginning, causing renal programming, has been linked to increased risk of hypertension and renal disease in adulthood. However, although a cause for concern, increasingly, evidence demonstrates that renal programming is not a fait accompli in terms of future cardiovascular and renal disease. A greater understanding of postnatal renal maturation and the impact of secondary factors (genes, sex, diet, stress, and disease) on this process is required to predict which babies are at risk of increased cardiovascular and renal disease as adults and to be able to devise preventative measures.
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Affiliation(s)
- Michelle M Kett
- Department of Physiology, Monash University, Clayton, Victoria, Australia
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Abitbol CL, Chandar J, Rodríguez MM, Berho M, Seeherunvong W, Freundlich M, Zilleruelo G. Obesity and preterm birth: additive risks in the progression of kidney disease in children. Pediatr Nephrol 2009; 24:1363-70. [PMID: 19214591 DOI: 10.1007/s00467-009-1120-2] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2008] [Revised: 11/23/2008] [Accepted: 12/15/2008] [Indexed: 11/28/2022]
Abstract
Preterm birth is associated with decreased nephron mass and obesity that may impact on kidney disease progression in later life. Our objectives were to examine the relative risks of obesity and preterm birth on the progression of kidney disease in children. In a retrospective cohort study, 80 (44 obese and 36 non-obese) patients with proteinuric kidney disease were studied for disease progression and glomerular histomorphometry. Of the obese, 22 had been born at term (Obese-T) and 22 had been preterm (Obese-PT). Seventeen non-obese children with focal glomerular sclerosis, born at term (NO-FSGS), and 19 non-obese preterm (NO-PT) children, served as controls. Insulin resistance as measured by the homeostatic model assessment (HOMA-IR) was elevated in all obese children. Obese-PT patients had increased risk of renal demise during childhood when compared with Obese-T children [hazard ratio 2.4; 95% Confidence interval (95% CI) 1.1 to 7.1; P = 0.04]. In obese children, although proteinuria often exceeded nephrotic range, average levels of serum albumin remained normal. Preterm patients were more likely to have reduced renal mass (odds ratio 4.7; P = 0.006), but obesity was not a factor. Renal histomorphometry showed glomerulomegaly in obese patients, regardless of birth weight. Obesity and preterm birth appear to impose additive risks for progression of kidney disease in childhood.
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Affiliation(s)
- Carolyn L Abitbol
- Division of Pediatric Nephrology (M714), University of Miami/Holtz Children's Hospital, 1611 NW 12th Avenue, Annex 5, Miami, FL 33126, USA.
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Hughson MD, Samuel T, Hoy WE, Bertram JF. Glomerular volume and clinicopathologic features related to disease severity in renal biopsies of African Americans and whites in the southeastern United States. Arch Pathol Lab Med 2007; 131:1665-72. [PMID: 17979484 DOI: 10.5858/2007-131-1665-gvacfr] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/11/2007] [Indexed: 11/06/2022]
Abstract
CONTEXT African Americans have a 4-fold greater risk than whites for developing end-stage renal disease. Glomerulomegaly, possibly related to obesity, has been identified in high-risk populations and is suggested to be a marker for end-stage renal disease risk. OBJECTIVE To investigate differences in glomerular size and patient clinical characteristics at the time of renal biopsy for the major diseases contributing to end-stage renal disease. DESIGN Mean glomerular tuft volumes were estimated by the Weibel-Gomez method (1964) in native renal biopsies of 203 African American and 100 white patients 18 years of age and older by point counting on a stereologic grid. Glomerulosclerosis was graded on individual glomeruli from 0 to 4, and a glomerular sclerosis index was calculated for each biopsy. Relationships between the mean volume of nonsclerotic glomeruli, age, sex, race, sclerosis index, cortical fibrosis, estimated glomerular filtration rate, body mass index, and disease diagnosis were analyzed. RESULTS Racial differences in mean volume of nonsclerotic glomeruli and body mass index were not significant in any disease category, and African Americans had more severe disease as determined by sclerosis index, cortical fibrosis, and estimated glomerular filtration rate only in focal segmental glomerulosclerosis. For all patients, increased sclerosis index and cortical fibrosis and lower estimated glomerular filtration rate were best predicted by increased age (P < .001). CONCLUSIONS For approximately the same severity of disease, African Americans were 10 years or more younger than whites with the difference being seen in all disease categories except membranous glomerulonephritis and diabetes. Glomerulomegaly relative to whites was not a distinguishing feature of African American renal biopsies.
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Affiliation(s)
- Michael D Hughson
- Department of Pathology, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216, USA.
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Samuel T, Hoy WE, Douglas-Denton R, Hughson MD, Bertram JF. Applicability of the glomerular size distribution coefficient in assessing human glomerular volume: the Weibel and Gomez method revisited. J Anat 2007; 210:578-82. [PMID: 17419811 PMCID: PMC2375741 DOI: 10.1111/j.1469-7580.2007.00715.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Changes in glomerular volume (V(glom)) play an important role in the initiation and progression of various glomerulopathies. Estimation of V(glom) in the normal kidney provides baseline values for studies of glomerular hypertrophy in disease. The traditional model-based method of Weibel and Gomez is widely applied to estimate V(glom) in clinical biopsy specimens. Assumptions of glomerular size distribution and shape required by this method are potential sources of bias that have not been verified. We evaluated the applicability of the glomerular size distribution coefficient in estimating V(glom) in human kidneys. V(glom) of 720 non-sclerotic glomeruli in histologically normal kidneys of 24 males (20-69 years) was estimated by the unbiased disector/Cavalieri approach. Accurate glomerular diameters were calculated from Cavalieri estimates of V(glom) assuming glomerular sphericity. The coefficients of variation (CV) of glomerular diameters were compared with the corresponding values of the size distribution coefficient predicted by the Weibel and Gomez method. Mean (SD) glomerular diameter was 201 (28) mm (range 110-276 mm). The CV of glomerular diameter within each kidney ranged from 4.9 to 14.6%. Corresponding glomerular size distribution coefficients predicted by the formula of Weibel and Gomez ranged from 1.00 to just 1.03. The value of the size distribution coefficient required by the Weibel and Gomez technique when estimating V(glom) in normal human kidneys is remarkably constant. This is despite large variations in V(glom). Future studies should examine the extent of bias introduced by the glomerular shape assumptions of this method.
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Affiliation(s)
- Terry Samuel
- Department of Anatomy and Cell Biology, Monash University, Melbourne, Victoria, Australia
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Korbet SM, Volpini KC, Whittier WL. Percutaneous renal biopsy of native kidneys: a single-center experience of 1,055 biopsies. Am J Nephrol 2004; 39:153-62. [PMID: 24526094 DOI: 10.1159/000358334] [Citation(s) in RCA: 95] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Accepted: 12/31/2013] [Indexed: 12/16/2022]
Abstract
BACKGROUND Percutaneous renal biopsy (PRB) of native kidneys is an essential tool in the diagnosis and management of renal disease. We report one of the largest single-center experiences on the success and safety of the procedure. METHODS From June 1983 to March 2012, 1,055 adults underwent PRB using real-time ultrasound guidance and 14-gauge biopsy needles. Data were collected prospectively for 826 biopsies (78%). Statistical analysis was performed using the Mann-Whitney test, Wilcoxon matched pairs test and Kruskal-Wallis test for continuous data or the Fisher's exact test and χ(2) test for categorical data. Multivariate analysis using logistic regression was performed to determine which feature at baseline was predictive of a complication following renal biopsy. RESULTS Patients were aged 46 ± 17 years; 38% were male, 40% were white and 43% were African-American. Serum creatinine (SCr) was 2.3 ± 2.3 mg/dl (>1.5 mg/dl in 47%). The pre-PRB hemoglobin was 12 ± 2 g/dl (<11.0 g/dl in 35%). Adequate tissue for diagnosis was obtained in 99% of biopsies. Minor complications occurred in 8.1% of biopsies (mainly gross hematuria, in 4.5%). Major complications occurred in 6.6% of biopsies, with transfusions required in 5.3%. Only 1 death (0.09%) resulted from post-PRB bleeding. By multivariate analysis, baseline features predictive of a complication were systolic blood pressure >170 mm Hg (OR 4.2, 95% CI 1.8-9.8), bleeding time >7.5 min (OR 1.7, CI 1.2-2.5) and SCr >3.5 mg/dl (OR 1.8, CI 1.2-2.9). CONCLUSIONS PRB of native kidneys using real-time ultrasound with a 14-gauge automated needle remains a successful and safe procedure.
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Affiliation(s)
- Stephen M Korbet
- Section of Nephrology, Department of Medicine, Rush University Medical Center, Chicago, Ill., USA
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