The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water (TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment (mainly sodium salts) and in the intracellular compartment (mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume (EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance.

This report describes our experience using a low-dose synthetic adrenocorticotropic hormone (ACTH) analog for patients affected by nephrotic syndrome who had not responded to or had relapsed after steroid and immunosuppressive treatments.

Eighteen adult nephrotic patients with an estimated glomerular filtration rate >30 mL/min were recruited. Histological pictures included ten of membranous nephropathy, three of membranous proliferative glomerulonephritis, three of minimal change, and two of focal segmental glomerular sclerosis. All patients received the synthetic ACTH analog tetracosactide 1 mg intramuscularly once a week for 12 months. Estimated glomerular filtration rate, proteinuria, serum lipids, albumin, glucose, and potassium were determined before and during the treatment.

One of the 18 patients discontinued the treatment after 1 month because of severe fluid retention, and two patients were lost at follow-up. Complete remission occurred in six cases, while partial remission occurred in four cases (55.5% responder rate). With respect to baseline, after 12 months proteinuria had decreased from 7.24±0.92 to 2.03±0.65 g/day (P<0.0001), and serum albumin had increased from 2.89±0.14 to 3.66±0.18 g/dL (P<0.0001). Total and low-density lipoprotein cholesterol had decreased from 255±17 to 193±10 mg/dL (P=0.01), and from 168±18 to 114±7 mg/dL (P=0.03), respectively. No cases of severe worsening of renal function, hyperglycemia, or hypokalemia were observed, and no admissions for cardiovascular or infectious events were recorded.

Tetracosactide administration at the dosage of 1 mg intramuscularly per week for 12 months seems to be an acceptable alternative for nephrotic patients unresponsive or relapsing after steroid-immunosuppressive regimens. Further studies should be planned to assess the effect of this low-dose ACTH regimen also in nephrotic patients not eligible for kidney biopsy or immunosuppressive protocols.

The effectiveness of intravenous methylprednisolone pulses in 20 mg/kg/day for three consecutive days was compared with a more conventional oral prednisone regime in inducing remission in adult patients presenting with first episodes of minimal change nephrotic syndrome. Methylprednisolone was significantly less effective and failed to induce remission in six of nine patients within two weeks of treatment, while the oral prednisone regime was uniformly effective in all eight patients within five weeks. Of the six non-responders to methylprednisolone five subsequently remitted with oral prednisone, and one with cyclophosphamide. Except for one patient in the oral prednisone group who had acute gastritis with bleeding, no serious side-effect was seen with either treatment regimes.

Thirty-seven percutaneous renal biopsies showing no significant abnormalities on light microscopy were studied electron optically and by immunofluorescence when available. Assessment of the pathological material was followed by analysis of the patients' clinical notes, and a clinicopathological correlation was carried out. Twenty-three patients fulfilled the clinical criteria of minimal change disease; 10 did not behave clinically as minimal change and showed immune complex deposition; two had benign recurrent haematuria; and two had myelomatosis. Our study shows that if diagnosis is based solely on the light microscope appearances of renal biopsy, diseases other than minimal change are likely to be overlooked. Accuracy of diagnosis in structural terms requires additional immunofluorescence and electron microscopic study; final clinical diagnosis also requires careful follow-up, and repeat biopsy may be necessary.

The experience with light microscopic examination of kidney biopsies in 150 children with nonspecific glomerulopathy is reported. Most major types of glomerular lesions, as they are at present known, were observed but in a very uneven distribution. Four groups of clinical symptoms were observed in the primary as well as in the associated non-specific glomerulopathies: hematuria, proteinuria, acute nephritic syndrome and nephrotic syndrome. Although in a number of instances, the histologic lesion was suggested by the clinical picture, a correlation was lacking in most instances. More information was obtained from the histology when the evolution was considered, particularly in the primary nephrotic syndrome and the Schönlein-Henoch nephropathy.

In a Cairo clinic 17 of 41 patients with chronic pyelonephritis secondary to urinary schistosomiasis presented with classical features of the nephrotic syndrome, two-thirds being hypertensive and the majority having glomerular filtration rates within the normal range. Hypercholesterolaemia was found in one-third of the patients. Urinary sediments from these patients contained a preponderance of pus cells, red cells, granular casts, or pus casts. In addition to patches of pyelonephritis, the glomeruli showed diffuse and focal glomerulosclerosis. Electron microscopy revealed basement-membrane-like deposits in the hypertrophied axial endothelial cells and electron-dense deposits along the glomerular basement membrane. This variety of nephrotic syndrome associated with schistosomal pyelonephritis was the most common cause of nephrotic syndrome seen in the clinic.