Reversible nephrotic syndrome in Crohn's disease complicated with renal amyloidosis

A 24-year-old woman suffered from ano-rectal Crohn's disease and nephrotic syndrome due to glomerular amyloidosis AA. She received azathioprine and colchicine for two years. Both Crohn's disease and nephrotic syndrome resolved. However amyloid renal lesions were still present. This course is exceptional, and leads to a discussion of the treatment of amyloidosis associated with Crohn's disease.     

The treatment of nephrotic syndrome caused by primary (light chain) amyloid with vincristine, doxorubicin and dexamethasone

Three out of four patients with primary (light chain) amyloid nephrotic syndrome treated with vincristine, doxorubicin and dexamethasone (VAD) induction obtained a partial response and are alive in continuing remission at 4.1, 6.5 and 9.3 years. These preliminary results are of considerable interest and suggest that prospective evaluation of this regimen is warranted in patients with this condition.     

Nephrotic syndrome associated with amyloid-like glomerular deposits

An Arab patient with a typical nephrotic syndrome associated with the deposition of an amyloid-like material in the glomeruli is described. The deposits consisted of an electron-dense finely granular material which contained immunoglobulins and complement and fibrillar structures which resembled those of amyloid but did not stain with the typical amyloid stains.     

Capillaries with fenestrations around regenerating muscle fibers in the soleus muscle of the dystrophic (dy) mouse

A 65-year-old woman developed nephrotic syndrome 7 years after receiving a cadaveric renal allograft. Renal biopsy and clinical laboratory evaluation revealed the underlying disease process to be AL amyloidosis. To our knowledge, this is the first reported case of de novo AL amyloid occurring in a renal allograft.     

Nephrotic syndrome in ulcerative colitis

Complicating disorders in various organs outside the intestinal tract are common in ulcerative colitis. This report deals with the occurrence of nephrotic syndrome in two patients with long-standing ulcerative colitis. In the patient studied in most detail, 2 episodes have taken place, the first developing into uremia. After colectomy had been performed, rapid improvement of renal function took place. The morphological changes in kidney biopsies were compatible with the presence of focal glomerular sclerosis. Activity in the complement system and a favorable response to steroid treatment indicate that humoral immune mechanisms are of pathogenetic importance with regard to the renal disease in these two patients. To our knowledge nephrotic syndrome has not previously been described as a complication to ulcerative colitis.     

Elevated lipoprotein (a) levels in primary nephrotic syndrome

Elevated plasma levels of total cholesterol and increase in the hepatic synthesis of some apo B-containing lipoproteins have been noted in the nephrotic syndrome. Apoprotein (a), the apolipoprotein distinguishing lipoprotein (a) [Lp(a)] from low-density lipoprotein, is equally of hepatic origin, and Lp(a) recently has been shown to possess both atherogenic and thrombogenic activities. However, little is known of Lp(a) levels in nephrotic patients. We measured plasma Lp(a) concentrations in 11 patients with primary nephrotic syndrome in the absence of hematuria, hypertension, and renal insufficiency. Histologic lesions were minimal-change disease in five cases, membranous glomerulopathy in four cases, and focal and segmental glomerulosclerosis in two cases. Mean levels of Lp(a) (98 +/- 92 mg/dL [mean +/- SD]) were markedly elevated in the nephrotic patients as compared with the controls (14 +/- 13 mg/dL). No correlation was noted between plasma Lp(a) and proteinuria, albuminemia, total cholesterolemia, low-density lipoprotein cholesterol, apoprotein B100, or plasminogen. Furthermore, there was no correlation between Lp(a) levels and apoprotein (a) isoform size. In four patients, the level of Lp(a) decreased approximately fourfold after remission of the nephrotic syndrome under corticosteroid treatment. Our observation that Lp(a) levels are elevated in the nephrotic syndrome is consistent with the hypothesis that these patients may be at an increased risk of cardiovascular and thrombotic complications.     

Cyclosporine in glomerular disease

Cyclosporine was introduced in 1981 as an immunosuppressive agent in renal transplantation. Its use was soon extended to the treatment of various glomerular disorders. In light of its known immunomodulating effects, the use of cyclosporine has been most prominent in those glomerular diseases thought to have an immune basis. The most careful studies of cyclosporine in glomerular diseases have been performed in the pediatric population with idiopathic nephrotic syndrome (i.e., minimal change disease and focal segmental glomerulosclerosis), although data are accumulating regarding efficacy and safety in adults with idiopathic nephrotic syndrome. In patients who are steroid-dependent, cyclosporine therapy can induce complete or partial remission in a significant proportion of cases; success rates in patients with steroid-resistant nephrotic syndrome are less encouraging. Treatment with cyclosporine allows for dose reduction or elimination of corticosteroids, and the consequent salutary effect on growth in the child and glucose and bone metabolism in all patients. Studies that suggest a potential benefit of cyclosporine in recurrent nephrotic syndrome in renal allografts and in other glomerular diseases are also discussed.     

Clinical and histologic findings in patients with renal amyloidosis

Renal amyloidosis is a rare disease when compared to other kidney diseases. During the period of last fifteen years, at the Institute of Nephrology and Immunology in Sarajevo renal amyloidosis was diagnosed with 15 patients. The disease occurred more often with men than with women. Only during 1988, renal amyloidosis was revealed and followed up with five patients. The most common clinical manifestations of renal amyloidosis are nephrotic syndrome and chronic renal failure, with respective laboratory findings. Using immunofluorescent analysis of the kidney biopsy material, we discovered deposits of immunoglobulins of different intensity and deposits of lambda and kappa light chains of immunoglobulins. The intensity of lambda light chains is greater than that of kappa chains. The analysis of light microscopy showed nodular mesangial deposits and deposits along GBM without proliferation. The diagnosis of amyloidosis was confirmed by staining of amyloid. Application of therapy for amyloidosis was without any effect. Although renal amyloidosis is a rare disease, we want to point out disease as being an etiologic factor in nephrotic syndrome.     

On the treatment of recurrent tonsillitis by vaccination

OBJECTIVE: To analyze the use of Cyclosporine (CyA) in nephrotic syndrome. METHODS: Thirty five children of mean age of 5.9 years with steroid dependent (n = 26) or steroid resistant (n = 9) primary nephrotic syndrome with normal renal functions and who received CyA were studied. CyA was used at a dosage of 6-7 mg/kg/day orally in two divided doses. The mean duration of therapy was 9.6 weeks. All received a minimum of 8 weeks of CyA therapy. In a few who received longer therapy, the dose was reduced to 4 mg/kg/day. All patients were monitored serially for hepatotoxicity and nephrotoxicity. The nephrotic state was evaluated serially with biochemical tests and followed up for a mean period of 2.55 years. RESULTS: Thirty one patients completed the study. The response to therapy was categorized into 5 groups-no response (4 patients), good response (4 patients), partial response (4 patients), cyclosporine dependence (16 patients), and infrequent relapsers (3 patients). Good response was defined as complete remission lasting for at least one year after cessation of therapy. Patients who showed partial response had reduction in quantitative proteinuria and needed less diuretics. Sixteen patients went into complete remission while on therapy but relapsed within 3 months of discontinuation (CyA dependence). The response to CyA correlated more with steroid-responsiveness than with the underlying histopathology. The drug was well tolerated. CONCLUSION: In steroid-dependent or steroid-resistant nephrotic children with normal renal functions, CyA therapy may be considered as one of the possible therapeutic options. Our results suggest that a longer duration of CyA therapy may possibly be indicated in these cases.     

Treatment of nephrotic adults with a supplemented, very low-protein diet

Optimal dietary protein intake for adults with the nephrotic syndrome has not been established; very low-protein diets are believed to be contraindicated. Sixteen patients with the nephrotic syndrome were nevertheless prescribed a very low protein diet (0.3 g/kg) supplemented by 10 to 20 g/d essential amino acids (or, in a few cases, ketoacids) for an average of 10 months (range, 1 to 36 months). In 11 patients with initial glomerular filtration rates (GFRs) < or = 30 mL/min/3 m2 of height (ht)2, significant but modest improvement was seen (on the average) in proteinuria, serum albumin, and serum cholesterol; all 11 eventually went on to dialysis. The other five patients, with initial GFRs of 32 to 69 ml/min/3 m2 of ht2, had either focal segmental glomerulosclerosis, diabetic nephropathy, or, in one patient, both. The nephrotic syndrome associated with these disorders rarely remits spontaneously. However, during the following 3 to 15 months mean proteinuria decreased from 9.3 to 1.9 g/d, mean serum albumin increased from 2.5 g/dL to 3.8 g/dL, and mean serum cholesterol decreased from 415 mg/dL to 255 mg/dL (all P < 0.001). The GFR either remained constant or increased. Four of these five patients have resumed normal or nearly normal diets and remain in remission or near-remission for 6 to 24 months. We conclude that severe protein restriction plus an essential amino acid supplement may induce prolonged remission in adults with the nephrotic syndrome provided that GFR is not severely reduced. The mechanism of this paradoxical response to protein restriction remains to be determined.     

Congenital nephrotic syndrome of the Finnish type is not associated with the Pax-2 gene despite the promising transgenic animal model

Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disease with an incidence of 1 in 8000 in Finland. CNF is characterized by massive proteinuria and nephrotic syndrome at birth. In a recent report, deregulation of expression of the gene coding for the Pax-2 DNA-binding protein was shown to generate severe kidney abnormalities in transgenic mice resembling the clinical and pathological findings in congenital nephrotic syndrome, making it a candidate gene for CNF. However, in this study, we have unequivocally excluded the Pax-2 gene locus as a causative for congenital nephrotic syndrome of the Finnish type.     

Renal dopaminergic system in nephrotic syndrome and after remission

BACKGROUND: Although intrarenal dopamine is known to behave as an endogenous natriuretic hormone the role of the renal dopaminergic system in the sodium handling of nephrotic oedema remains unknown. STUDY DESIGN: We monitored the daily urinary excretion of free dopamine, L-DOPA-its precursor, and its metabolites, DOPAC and HVA, during sodium retention accompanying the nephrotic state and natriuresis leading to oedema mobilization in eight patients (mean age 8.0+/-2.4 years) with drug-induced remission of minimal-change nephrotic syndrome (MCNS). RESULTS: During natriuresis the urinary levels of dopamine did not increase in parallel with sodium excretion in any of the eight patients studied. Moreover, after remission of the nephrotic syndrome the urinary levels of dopamine were significantly lower than during the nephrotic state (1565.3+/-361.7 vs 2416.1+/-558.4, P= 0.02). In contrast, the urinary excretion of L-DOPA increased markedly during natriuresis resulting from remission of proteinuria (from 87.0+/-40.5 up to 296.9+/-86.3 nmol/24 h; P< 0.01). CONCLUSION: We conclude that the natriuretic response resulting from drug-induced remission of proteinuria in MCNS is accompanied by a decrease in the renal uptake/decarboxylation of L-DOPA to dopamine.     

New taxane diterpenoids from the roots of Taxus mairei

OBJECTIVE: We tested the hypothesis that nitric oxide synthesis by the kidney is increased in children with primary nephrotic syndrome. METHODS: We examined the urinary excretion of nitrite, a stable metabolite of nitric oxide, using the Griess reaction, in children with nephrotic syndrome. RESULTS: In comparison with healthy children, patients with minimal change nephrotic syndrome had increased urinary nitrite excretion regardless of whether the disease was in relapse or remission (p < 0.025). In contrast, urinary nitrite excretion was similar in control subjects and patients with focal segmental glomerulosclerosis or IgA nephropathy. CONCLUSION: These findings indicate that measurement of urinary nitrite excretion may be a useful test to help discriminate between minimal change nephrotic syndrome and focal segmental glomerulosclerosis in children with idiopathic nephrotic syndrome.     

What's new in pediatric nephrology?]

Advances in pediatric nephrology has been mainly characterized during the last years by a burst of knowledge in the area of genetic renal diseases: 1/almost complete understanding of Alport syndrome related to mutations of COL4A5 or COL4A3/A4 genes of collagene; 2/the mapping and cloning of the nephronophthisis gene which is deleted in 75% of cases; 3/the mapping and cloning of the cystinosis gene coding for a protein of the lysosomal membrane; 4/the mapping and cloning of the Finnish-type congenital nephrotic syndrome gene; 5/the linkage to the SNR 1 gene on chromosome 1 of a large number of familial corticoresistant nephrotic syndromes, and the disclosure of mutations of the WT1 gene in diffuse mesangial sclerosis and in Frazier syndrome. The understanding of Bartter syndrome has been also enlightened by the discovery of mutations in several ionic channels located in the distal tubule. It has been also shown that a corticoresistant nephrotic syndrome or a chronic tubular interstitial nephropathy are possible phenotypes for mitochondrial cytopathies. In the area of therapeutics, recombinant growth hormone was shown to improve statural growth of children with chronic renal failure; in addition, renal transplantation benefits from new immunosuppressants as tacrolimus and mycophenolate mofetil.     

Laboratory findings and serum levels of amyloid A and soluble interleukin-2 receptors in patients with renal amyloidosis

BACKGROUND: Renal amyloid involvement results either from primary or secondary amyloidosis. Extent of amyloid tissue deposition in kidneys and clinical course depends not only on the type of basic process but reflects also time of diagnosis and possibility to influence the basic process. METHODS AND RESULTS: We analyzed laboratory and clinical data of patients with bioptically proven renal amyloidosis. We found renal amyloidosis in 27 patients from an overall number of 750 renal biopsies (RB) performed in our department (i.e. 3.6%). AA amyloidosis was diagnosed in 16 pts, AL amyloidosis in 11 pts. About 50% of patients had laboratory signs of nephrotic syndrome, all patients had various degree of proteinuria. Impaired renal function were found in more than 50% of patients, in 6 of them we had to start renal replacement therapy. 8 pts died. Complications of severe nephrotic syndrome were the causes of death in majority of cases. We have started investigation of some amyloid precursors and cytokines in patients with AA and AL amyloidosis. We compared the results with group of patients with vasculitis. We investigated plasma and urinary levels of SAA (serum AA) and soluble receptor for interleukin 2 (sIL-2R). CONCLUSIONS: Clinical features and laboratory findings in our patients with renal amyloidosis approximately are in accordance with literary data. Plasmatic level of SAA was increased not only in the group of patients with AA amyloidosis, but also in the group of vasculitis. Urinary sIL-2R was significantly increased in patients with AA amyloidosis in comparison with healthy controls.     

Monoclonal IgE with renal failure

Only four cases of immunoglobulin E (IgE) monoclonal "gammapathies" have been reported previously. Discussed here is a 57 year old man who presented with hypertension and the nephrotic syndrome. A monoclonal IgE-kappa component (0.6 mg/ml), which did not appear as an M spike on protein electrophoresis, was demonstrated by immunoelectrophoresis in the serum and urine. The patient's condition deteriorated rapidly due to renal failure, and he died five weeks after the diagnosis was made. Pathologic examination disclosed extensive glomerular lesions, but amyloid was not detected by light or electron microscopy. The possible relationship between the monoclonal gammapathy and kidney impairment is discussed.     

Management of hyperlipidemia in children with refractory nephrotic syndrome: the effect of statin therapy

The efficacy and safety of hydroxymethylglutaric coenzyme A reductase inhibitor (statins) in the treatment of hyperlipidemia were evaluated in 12 infants and children with steroid-resistant nephrotic syndrome followed prospectively for 1 to 5 years. All patients experienced a hypolipidemic response with a marked reduction in their total cholesterol (40%), low-density lipoprotein cholesterol (44%), and triglyceride levels (33%), but no appreciable change in high-density lipoprotein cholesterol. Statin therapy was well tolerated without clinical or laboratory adverse effects. In spite of a significant hypolipidemic response to statin therapy there were no changes observed in the degree of proteinuria, hypoalbuminemia, or in the rate of progression to chronic renal failure. Long-term controlled studies with statin therapy are needed to further document or negate their renoprotective role in refractory nephrotic syndrome.     

Multicentric Castleman''s disease with mediastinal involvement in a patient with HIV infection]

Congenital nephrotic syndrome of Finnish type is a rare disease in Taiwan characterized by intrauterine onset of massive urinary loss of protein. We describe a typical baby of congenital nephrotic syndrome with generalized edema occurring at 3 months of age. Renal biopsy at 4 months of age showed a tubular microcystic change in histology. He had a partial response to corticosteroid. We tried persantin, indomethacin, and captopril since 10 months of age without significant improvement. The baby suffered from recurrent infections and respiratory difficulties due to having upper airway edema since 3 months of age. The baby passed away at 1 year and 2 months of age with severe psychomotor retardation. The first try of the combination of persantin, indomethacin, and captopril for congenital nephrotic syndrome is described.     

Lipid peroxidation and the system of antioxidant protection in patients with chronic glomerulonephritis and normal kidney azoturic function

As indicated by blood tests, chronic glomerulonephritis (CGN) patients with intact renal function have impaired lipid peroxidation and antioxidant defense. In nephrotic syndrome these plasm changes are more pronounced, but red cells remain relatively intact. Persistent nephrotic syndrome produces a trend to shifts in red blood picture. In CGN patients free of nephrotic syndrome red cells exhibited lipid peroxidation and weak antioxidant defense. The above facts support the validity of antioxidants use in combined treatment of CGN.     

Transport of LDS-751 from the cytoplasmic leaflet of the plasma membrane by the rhodamine-123-selective site of P-glycoprotein

Hyperfibrinogenemia is a common feature of the nephrotic syndrome, and contributes to increased tendency for thrombosis and atherosclerosis. Its genesis is not certain, but the increase in liver fibrinogen mRNA in nephrotic rats indicates increased synthesis. Data in humans are scarce. We presently compared synthesis rates of fibrinogen and albumin in nephrotic adults (N = 7; plasma albumin 22.3 +/- 0.7 g/liter, proteinuria 12 g/day) and healthy control subjects (N = 8) using a primed/continuous infusion of the stable isotope L-[1-13C]valine for six hours. Absolute synthesis rate (ASR) of fibrinogen was 31 +/- 3 mg/kg/day in nephrotic subjects and 21 +/- 1 mg/kg/day in control subjects (P < 0.05), and positively correlated with plasma fibrinogen (P = 0.0317). The plasma fibrinogen pool was disproportionately increased in the nephrotic patients (271 +/- 30 mg/kg) compared to the controls (126 +/- 8 mg/kg), suggesting decreased fractional catabolic rate as well. The ASR of albumin was increased from 71 +/- 4 mg/kg/day in the controls to 160 +/- 19 mg/kg/day in the patients (P < 0.0001), and strongly correlated with the ASR of fibrinogen (P = 0.0046). Plasma alpha 2-macroglobulin was also elevated and correlated with the albumin synthesis rate, whereas plasma serum amyloid A and C-reactive protein were not elevated. These data suggest that in nephrotic patients the increased albumin synthesis is associated with an increase in synthesis of a specific and coordinated group of proteins, among which is fibrinogen.