Minimal Change Glomerulopathy Research Articles

Nephrotic Syndrome Associated With a Clonal T-Cell Leukemia of Large Granular Lymphocytes With Cytotoxic Function

A 51-year-old man presented with a T-cell leukemia of large granular lymphocytes and rapidly developed a nephrotic syndrome due to presumptive minimal-change glomerulopathy. The E-rosette+, Ia+ cells demonstrated cytotoxic activity similar to that of natural killer lymphocytes but lacked other T-subset markers, except that one third of them bore Fc(IgG) receptors. Cytogenetic analysis revealed loss of chromosome 10 and the translocation (1;10)(p11;q11) in all metaphases. Regression of the leukemia after chemotherapy was accompanied by a dramatic resolution of the nephrotic syndrome, suggesting that the activated granular lymphocytes induced the renal lesion. The close association of a clonal T-lymphoproliferative disorder with minimal-change nephrotic syndrome lends further support to current views implicating activated T cells or their products in the pathogenesis of this glomerulopathy.

Glomerulopathy does not increase renal susceptibility to acute ischemic injury.

To determine whether preexistent glomerular injury and the nephrotic syndrome increase renal susceptibility to ischemic renal injury, normal rats and rats with either experimental minimal-change disease (Adriamycin nephropathy) (AN) or membranous nephropathy (passive Heymann nephritis) (PHN) underwent renal functional and histologic studies under either basal conditions or 18 h after bilateral renal artery occlusion (over 30 min). Prior to renal ischemia AN and PHN rats had minimally depressed glomerular filtration rate (GFR), normal (AN) or increased (PHN) renal blood flow (RBF), heavy proteinuria, hypoalbuminemia, decreased urine sodium excretion, extensive glomerular foot process fusion, and intratubular hyalin cast formation. Losses of GFR in response to ischemia were comparable among the three groups of rats (controls, 0.29; AN, 0.28; PHN, 0.25 ml X min-1 X 100 g body wt-1) despite prevailing differences in postischemic hemodynamics. Neither light nor transmission electron microscopy showed any differences in the degree of ischemic renal injury. These results suggest that 1) glomerulopathy and the nephrotic syndrome do not significantly increase renal susceptibility to ischemic renal injury; 2) the syndrome of acute renal failure that occurs in patients with minimal-change glomerulopathy is not due to a marked susceptibility of these kidneys to clinically occult ischemic events; and 3) foot process fusion is probably not a pathophysiologically significant lesion in ischemic acute renal failure, as previously suggested.

T and B lymphocyte subsets in fenoprofen nephropathy

Renal failure due to combined acute interstitial nephritis and minimal-change glomerulopathy is reported in two patients after fenoprofen therapy. In the interstitial infiltrates, T lymphocytes predominated over B lymphocytes in a ratio of four to one. The majority of B lymphocytes present were IgE-bearing cells. Among the T cells, the ratio of cytotoxic/suppressor cells to helper-inducer cells was three to one. Repeated renal biopsy in one patient after steroid-induced clinical remission demonstrated resolution of the inflammatory infiltrate and restoration of normal glomerular foot processes. The theoretic and practical implications of these findings are discussed.

Sulindac and Renal Impairment-Reply

In Reply.— The patient described by Whelton et al manifests both interstitial nephritis and nephrotic syndrome most likely caused by sulindac. This occurred after 36 months of treatment and resolved over several months after the drug therapy was discontinued. In our article, we noted four major types of renal toxicity on NSAID therapy: interstitial nephritis, minimal-change glomerulopathy, papillary necrosis, and functional changes in renal blood flow and glomerular filtration rate secondary to inhibition of prostaglandin synthesis. The first three types are rare, occur after weeks or months of NSAID therapy, and take extended periods to resolve. The mechanism in the first two types seems to be immunologically mediated, with lymphocytes playing a major role. 1,2 The combined presence of interstitial nephritis and minimalchange glomerulopathy in the patient of Whelton and co-workers is a characteristic of NSAID nephropathy. The renal toxicity emphasized in our article appears within several days, is frequently

Minimal-Change Nephropathy and Malignant Thymoma

A 56-year-old man had fever, precordial pain, and a mediastinal mass. The mass disappeared two months later and the patient remained asymptomatic for 2 1/2 years. At that time a full-blown nephrotic syndrome developed, with minimal-change glomerulopathy. The chest x-ray film showed the reappearance of a giant mediastinal mass. On biopsy of the mass, malignant thymoma was diagnosed. Association between minimal-change disease and Hodgkin's disease is well known, while the association with malignant thymoma has not been previously reported. The relationship between malignant thymoma and minimal-change disease is discussed, and a possible pathogenic mechanism involving cell-mediated immunity is proposed.