N-acetylcysteine prophylaxis significantly reduces the risk of radiocontrast-induced nephropathy: comprehensive meta-analysis.

The objectives of this study was to assess the overall effect of N-acetylcysteine (NAC) in preventing radiocontrast-induced nephropathy (RCIN) using all available data in the literature. RCIN is associated with increased morbidity and mortality. Existing randomized trials of NAC are small and show inconsistent results. Prior meta-analyses do not include data from the most current studies. We used standard search protocols to identify all published articles and abstracts of prospective trials using NAC with fluid hydration compared to hydration alone in patients with chronic renal insufficiency undergoing contrast procedures. A rise in serum creatinine by 0.5 mg/dl or 25% above baseline at 48-72 hr after contrast exposure was used as the primary outcome. We identified 14 trials of NAC with 1,584 patients published as full-text articles. Using a random-effects model, the use of oral NAC resulted in a significant reduction in the risk for developing RCIN (RR = 0.57; 95% CI = 0.37-0.84; P = 0.01). This finding did not significantly change in a fixed-effect model (RR = 0.55; 95% CI = 0.42-0.73) or when the data were reanalyzed using only randomized trials in all forms (i.e., articles and abstracts; RR = 0.67; 95% CI = 0.47-0.95). We identified only one important difference between the positive and the negative studies: the cumulative exposure to contrast media (174 vs. 152 ml). Metaregression did not show a significant relationship between contrast volume and the RR of developing RCIN (P > 0.10). In the trials showing benefit for NAC, the treated patients' postprocedure creatinine unexpectedly decreased by 0.21 mg/dl (95% CI = 0.33-0.08). Prophylaxis with NAC significantly reduces the risk for RCIN. The reasons for improvement in serum creatinine in patients treated with NAC are unclear, but may include improved renal blood flow due to NAC and/or vigorous hydration.     

Long-term follow-up study of 268 diabetic patients undergoing haemodialysis, with special attention to visual acuity and heterogeneity

We studied the long-term outcome of 268 patients suffering fromdiabetic end-stage renal disease (DM-ESRD) treated with long-termhaemodialysis between 1978 and 1991, with special emphasis onvisual acuity as well as the heterogeneity of DM-ESRD The 50%patient survival on haemodialysis was 60 months. Visual disturbanceswere found in 73.1% (392/536) of eyes at the start of haemodialysis.Chronological assess ment of visual acuity demonstrated thestabilization of visual acuity and 87.1% (364/418) of eyes werestable, 4.8% (20/418) were improved, and 8.1% (34/418) wereaggravated in the long term respectively. The change of visualacuity was frequently seen in the short term, and rapid shiftsof body fluid to correct overhydration induced abrupt changesof glycaemic control as well as retraction of macular oedema.Hence it might be one of the factors affecting rapid changeof visual acuity in the short term. Meanwhile, long-term deterioration of visual acuity resulted from either hyperten sionunresponsive to medical treatment or poor glycaemic control.Some DM-ESRD patients had only background retinopathy at thestart of haemodialysis and these were likely to have the nephroscleroticglomerular lesion. They were old, not nephrotic and had a milddegree of diabetes during the predialysis stage. Thus, DM-ESRDpatients seem to have some heterogeneity in their clinical characteristics,and old DM-ESRD patients with only background retinopathy havethe appearance of diabetic macroangiopathy rather than microangiopathy.     

Angiotensinogen gene M235T polymorphism is not associated with diabetic nephropathy

BACKGROUND.: There is agreement that a family history of hypertension (HT),is a predictor for the risk of diabetic nephropathy (DN) inpatients with type 2 diabetes, and possibly also type 1 diabetes.It follows that genes related to the risk of hypertension mustalso be considered candidate genes for DN. The 235T allele ofthe angiotensinogen gene was found to be related to primaryHT. METHODS.: To examine whether it is predictive for DN as well, we examinedthe angiotensinogen gene polymorphism in 230 healthy local controls,423 patients with type 1 diabetes (n=180 with DN; n=243 withoutDN) and 663 patients with type 2 diabetes (n=310 with DN; n=353without DN). The angiotensinogen gene M235T polymorphism wasdetermined using PCR amplification. RESULTS.: The following results were obtained (i) no significant differenceof genotype distribution (type 1: MM/MT/TT(%) 27.6/57.2/15.2vs. 27.2/56.1/16.7 (P=0.92); type 2: MM/MT/TT (%) 31.7/48.2/20.1vs. 32.9/46.8/20.3 (P=0.93)) or allele frequencies (type 1:M 0.56 vs. 0.55 (P=0.795); type 2: M 0.56 vs. 0.56 (P=0.86))was found, between diabetic patients with or without DN, (ii)no difference was found between normotensive and hypertensivediabetic patients. CONCLUSION.: The data argue against a role of the angiotensinogen gene M235Tpolymorphism in the manifestation of diabetic nephropathy orhypertension in diabetic patients.     

Dietary factors and progression of diabetic nephropathy

The role of dietary factors in patients with type 1 (insulin-dependent) diabetes is reviewed by examining three different aspects: the effect of an acute protein load, the effect of dietary protein restriction on the progression of nephropathy and the metabolic effects of low-protein diets. After an acute protein load some impairment of the renal functional reserve may be observed only in patients with type 1 diabetes and overt nephropathy. However, the renal functional reserve is not able to give useful indications of the extent of renal damage and the prognosis of the disease. Both short-term and long-term dietary protein restriction are followed by a significant decrease in glomerular filtration rate (GFR) and albuminuria in type 1 diabetics with incipient nephropathy. In patients with overt nephropathy the long-term administration of a low-protein diet is followed by significant reductions in the rate of decline of GFR and in urinary protein excretion only when started at GFR values higher than 45 ml/min. The rate of functional deterioration when dietary treatment is prescribed seems critical in modulating the effects of a low-protein diet. In addition, low-protein diets may exert important metabolic and clinical effects beyond their supposed effect on progression. Clearly, an adequate dietary regimen is only part of the medical treatment in patients with diabetic nephropathy.     

Reversible changes of visual acuity and pattern-electroretinograms after blue-green argon laser photocoagulation of diabetic patients

Visual acuity, color vision, pattern-visual-evoked-potentials (P-VEPs) and pattern-electroretinograms (P-ERGs) were measured in 13 diabetic subjects before, and 24 hours and 5 weeks after blue-green argon laser treatment. As control, the same examinations were performed in 7 normal subjects and 7 diabetic patients before and after slit lamp examination with the Goldman three mirror contact lens.Visual acuity and P-ERG amplitudes were significantly reduced one day after the laser treatment, while 5 weeks after the laser coagulation, visual acuity and P-ERG amplitudes recovered to pretreatment values. The control group showed no significant changes after slit lamp examination. Since fluorescein angiography revealed no macular changes after laser treatment, the possibility of a reversible functional light damage after blue-green argon laser coagulation (ALC) is discussed.This study was supported by the Medizinisch - Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien.     

Alpha-SM actin expression as prognostic indicator in IgA nephropathy (Berger's disease)

Recent studies have demonstrated that α-Smooth Muscle actin expression in glomerular and tubulointerstitial compartments of renal tissue could represent a prognostic marker in several renal diseases. Our objective was to identify the prognostic value of α-SM actin actin expression on the evolution of renal damage in Primary IgA nephropathy (Berger’s Disease). 43 patients followed up from 1988 to 1999 at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil, was studied. Clinical-laboratory data were obtained from the medical records of the patients using a protocol containing name, race, gender, origin, profession, age at clinical presentation of the disease and personal and family history. The parameters assessed in the approach to IgA nephropathy were serum creatinine, creatinine clearance, serum albumin, total serum protein, 24 hours proteinuria, glycaemia, serum sodium, potassium, calcium and phosphorus ions, analysis of urinary sediment, serum complement profile, blood count, and renal biopsy. Morphological evaluation was performed by renal biopsy using common light and immunofluorescence microscopy. Immunohistochemical studies were performed using a murine monoclonal antibody to α-SM actin. Our data showed that α-SM actin expression in the glomerular and tubulointerstitial compartments are not correlated with unfavorable clinical course of primary IgA nephropathy.     

IgA polyspecific autoantibodies in IgA nephropathy.

The specificity of circulating and kidney-bound IgA during IgA nephropathy is still a matter of discussion. In the present study, high levels of IgA antibodies directed against a panel of self and non-self antigens were found in the serum from patients with IgA nephropathy and were eluted from four out of the seven kidney biopsies studied. After immunoadsorption of pooled selected serum samples on TNP and actin-coated columns, polyspecific IgA antibodies were eluted. This supports the hypothesis that IgA-bearing B cells clones most probably producing polyspecific antibodies are a major feature of human IgA nephropathy. These findings also suggest that it may be hazardous to draw conclusions from the finding of apparently monospecific IgA antibodies in this condition.     

Glomerular changes in BK virus nephropathy

This study seeks to define the glomerular changes that are associated with human BK virus nephropathy (BKVN). It is based on histopathologic review of 124 biopsies showing light-microscopic changes of viral nephropathy. The diagnosis of BKVN was confirmed by immunohistochemistry or by in situ hybridization. Histological lesions were scored by the Banff 97 criteria for renal allograft pathology and were correlated with clinical parameters. Viral cytopathic effect in the parietal Bowman's capsular epithelium was seen in 21/124 (17%) biopsies. Immunohistochemistry showed infection of Bowman's capsular epithelium in an additional 15/124 (12%) biopsies. Crescents were found in 15/124 (12%) samples. Glomerulitis exceeding grade Banff g1 was only occasionally shown (4/124=3% biopsies). Other pathologic lesions documented include mild increase in mesangial matrix in 23% biopsies, aneurysmal dilatation of glomerular capillaries in 28%, ischemic glomerulopathy in 62%, and chronic transplant glomerulopathy graded as mild (cg1) in 62% of biopsies and as moderate (cg2) in 2/124 (1.9%) biopsies. These findings show that infection of the glomerular epithelium cells can occur in a subset of patients with BKVN, most often in biopsies with high viral load in the tubular epithelium. Isolated crescents can occur in BKVN biopsies, but rapidly progressive glomerulonephritis is not observed. Two biopsies showed electron-dense deposits on ultrastructural examination, but a cause and effect relationship to BK virus infection could not be established.     

Imbalances in serum proinflammatory cytokines and their soluble receptors: a putative role in the progression of idiopathic IgA nephropathy (IgAN) and Henoch–Schönlein purpura nephritis,and a potential target of immunoglobulin therapy?

Following recent experimental data suggesting an aggravating effect of circulating proinflammatory cytokines on the histological lesions of IgAN, we studied changes in serum proinflammatory cytokines and their soluble receptors and antagonists in patients treated with polyvalent immunoglobulins (15 with severe nephropathy who had indicators of poor prognosis: heavy proteinuria, hypertension, altered renal function and Lee's histological grade III or IV; and 14 with moderate forms of IgAN who had permanent albuminuria > 300 mg/day and < 2000 mg/day, Lee's histological grade II and a glomerular filtration rate > 70 ml/min) in comparison with healthy controls (n = 20) and patients with non-IgA nephritides (n = 50). These were measured by means of specific immunometric assays before and after 9 months of immunoglobulin therapy. Total tumour necrosis factor (TNF) serum and IL-6 levels were elevated in IgAN patients before therapy, relative to controls, and normalized after immunoglobulin therapy. Levels of soluble TNF receptor of type I (sR55) and type II (sR75) increased on immunoglobulin therapy. TNF index α-55,75 used to assess biologically available TNF-α (ratio of total TNF-α divided by levels of soluble TNF receptors sR55 and sR75) was elevated before therapy and was below healthy control values after 9 months of immunoglobulin administration. Levels of serum IL-1 receptor antagonist were low prior to immunoglobulin administration in patients with severe forms of IgAN, and normalized on therapy. Serum interferon-gamma was unmodified. The histological activity index correlated with serum total TNF-α, TNF index α-55,75 and serum IL-6 levels, whereas proteinuria correlated with serum total TNF-α and TNF index α-55,75 but not with serum IL-6. These data suggest that the overproduction of proinflammatory cytokine is unbalanced by their natural antagonists in IgAN and Henoch–Schönlein syndrome. This process may play a role in the progression of the disease and be one of the targets of immunoglobulin therapy.     

The nephronophthisis complex

Summary The clinical and morphological findings are described in 27 children with nephronophthisis. Seventeen children were considered as sporadic cases. In 10 familial cases the presumed mode of inheritance was autosomal recessive. The clinical picture was rather uniform: polyuria-polydipsia, hyposthenuria, anemia, growth retardation, and azotemia with progressive renal failure. Six patients presented with tapeto-retinal degeneration. In a further seven children other ocular changes were detected. Two female siblings showed additional non-renal manifestations: mental retardation, pulmonary emphysema, skeletal anomalies, and congenital hepatic fibrosis.Renal histology displayed a chronic sclerosing tubulo-interstitial nephropathy with extensive tubular atrophy and dedifferentiation. Medullary cysts were frequently found in end-stage kidneys. Immunofluorescence was either non-specific or completely negative. On electron microscopy, the tubular basement membrane changes predominated: thickening, lamellation, splitting, and deposition of microfibrils within the increased basement membrane substance. Detailed light- and electron microscopic findings were non-specific but the overall morphologic picture was characteristic and even diagnostic in conjunction with the clinical presentation.A recurrence of nephronophthisis in transplanted kidneys has not been observed.The pathogenesis of nephronophthisis is obscure but with respect to the morphologic findings a primary or secondary tubular basement membrane defect seems very likely.Our experience suggests that nephronophthisis is a frequent cause of chronic renal failure in children and commonly associated with non-renal abnormalities. To avoid the separation of different syndromes presenting with a uniform renal disease but various non-renal manifestations, we suggest that the term nephronopthisis complex be used.Presented in part at the 63th Annual Meeting of the German Society of Pathology, Stuttgart 1979