[Practice guideline and trends for immunosuppressive treatment of glomerulonephritides according to KDIGO (Clinical Practice Guideline for Glomerulonephritis)]. / Doporucené postupy a trendy v imunosupresivní lécbe glomerulonefritid podle KDIGO (Clinical Practice Guideline for Glomerulonephritis).

We summarize recommendations for glomerulonephritis treatment, established by internationally recognized experts in the field and sponsored by KDIGO (Kidney Disease Improving Global Outcomes). Up till now, the KDIGO review has been the most prestigious analysis of therapeutic trials on immunosuppressive treatment of glomerulonephritides. The 167 recommendations addresses the following forms of glomerulopathies: steroid-sensitive nephrotic syndrome and steroid resistant nephrotic syndrome in children; minimal change disease and idiopathic focal segmental glomerulosclerosis in children and adults; idiopathic membranous nephropathy; idiopathic membranoproliferative glomerulonephritis; glomerulonephritis associated with infection; immunoglobulin A nephropathy and Henoch-Schönlein purpura nephritis; lupus nephritis; pauci-immune focal and segmental necrotizing glomerulonephritis; and anti--glomerular basement membrane antibody glomerulonephritis. We focused our attention on progress in this topic in the last decade.

[To salt or not to salt in kidney diseases? Not more than quantum satis!]. / Solit nebo nesolit pri ledvinových chorobách? Ne více nez quantum satis!

The salt intake in former Czechoslovakia is twice as high as recommended 5 g/24 hours, which corresponds to 85 mmol//24 hours of sodium in the urine. In the population, the systemic blood pressure level correlates with a urinary excretion of sodium/24 hours. On the other hand, limited salt intake decreases blood pressure in salt-sensitive hypertensive patients. Albuminuria also positively correlates with a salt intake in the population. In patients with renal disease, a diet with low salt content suppresses proteinuria, and, in contrast, proteinuria is elevated with increased salt intake. The positive influence of the decreased salt intake on the progression of renal insufficiency was confirmed in many experimental studies. However, in humans, this finding was not unequivocally established in control randomized studies. The high salt intake worsens metabolic acidosis in patients with renal insufficiency. Salt is detrimental to the kidneys either by increased systemic and intraglomerular blood pressures or by pressure independent mechanisms of the tissue injury, which are mediated by a higher sodium concentration. The present knowledge concerning the relationship between sodium intake and extracellular fluid volume probably will be modified in light of new discoveries about the osmotically inactive sodium. The public enlightenment and medical application of these new findings related to harmful effects on an inappropriate salt intake in treatment of the kidney disease and in other fields of medicine is strongly desirable.

[End stage of chronic kidney disease and metabolic acidosis]. / Konecné stadium chronického onemocnení ledvin a metabolická acidóza.

Renal function disorder is inevitably associated with metabolic acidosis. An adult produces approximately 1 mmol of acids/kg of body weight every day (3 mmol/kg in children), derived from metabolization of proteins from food. Development of metabolic acidosis in patients with kidney disease is based on accumulation of acids and insufficient production of bicarbonates; alkaline loss represents a marginal issue here limited to patients with type II renal tubular acidosis only. The prevalence of this disorder increases with declining glomerular filtration (GFR) from 2% in patients with GFR 1.0-1.5 ml/s/1.73 m2 to 39% in patients with GFR < 0.3 ml/s/1.73 m2 or, alternatively, to 19% in patients with GFR 0.25-0.3 ml/s/1.73 m2. Notwithstanding the primary cause of the renal disease, declining GFR is associated with compensatory increase in ammoniac production in residual nephrons. This is an adaptive mechanism aimed at maintaining sufficient elimination of acids despite reduced volume of functional tissue. However, an increased ammoniac production simultaneously becomes a stimulus for activation of the complement via an alternative route and is thus one of the factors contributing, through this induced inflammation, to progression of tubular interstitial fibrosis that subsequently leads to further GFR reduction. Metabolic acidosis has a number of severe adverse effects on the organism, e.g. deterioration of kidney bone disease through stimulation of bone resorption and inhibition of bone formation, inhibition of vitamin D formation, increased muscle catabolism, reduced albumin production, glucose metabolism disorder, increased insulin resistance, reduced production of thyroid hormones, increased accumulation of ß2-microglobulin etc. Non-interventional studies suggest that alkali supplementation may slow down progression of chronic nephropathies. However, this approach, safe and inexpensive, has not been widely implemented in clinical practice yet. With respect to dialyzed patients, abnormal levels of bicarbonates are associated with increased mortality. Both metabolic acidosis and alkalosis, rather regularly seen in a considerable number of patients, have a negative effect on patient survival. Alkali substitution from a dialysis solution is the main pillar of metabolic acidosis management in patients on hemo- as well as peritoneal dialysis. Available technologies allow individualization of the treatment and this should be observed.

[Pathophysiology of metabolic acidosis in patients with reduced glomerular filtration rate according to Stewart-Fencl theory]. / Patofyziologie vzniku metabolické acidózy u pacientu se snízenou glomerulární filtrací z hlediska Stewartovy-Fenclovy teorie.

AIM: Metabolic acidosis is a regular sign of renal insufficiency. Conventional assessment of acid-base balance using Henderson-Hasselbalch equation does not make identification of the cause of metabolic disorders possible as the serum HCO3- concentration might only reflect changes to the overall plasma ion spectrum. Therefore, we used the Stewart-Fencl approach that is based on a more detailed physical and chemical analysis and that showed that changes to serum HCO3- concentration are closely related to parameters not usually monitored in connection to acid-base balance. PATIENT GROUP AND METHODOLOGY: We performed a single measurement of arterial or capillary blood pH and pCO2 in 69 non-dialysed patients with glomerular filtration rate ranging from 0.04 to 0.88 ml/s/1.73 m2 according to MDRD, standard calculation of serum HCO3- concentration using Henderson-Hasselbalch equation was carried out, and serum albumin and ion concentrations (Na+, K+, Cl, Pi) plus creatinine and urea concentrations were determined from venous blood. RESULTS: Metabolic acidosis was present in 47 patients ([S-HCO3-] < 22 mmol/l) with the mean [S-HCO3-] value of 19.6 mmol/l for the entire group. We proved a statistically significant correlation between [S-HCO3-] and [SID] (p < 0.001), and between [S-HCO3-] and the individual [SID] determining factors: [Na+-Cl-], [UA- ], [Pi-], [K+] (p < 0.01). CONCLUSION: Reduction in [S-HCO3-] in non-dialysed patients with reduced glomerular filtration is predominantly associated with a decrease in [Na+-Cl-] difference, the quantitative contribution of which to metabolic acidosis is more significant than the strong acids retention. In addition to [S-Cl-] increase, [S-Na+] reduction too has a major role in reducing the [Na+-Cl-] difference.

Role of aberrant glycosylation of IgA1 molecules in the pathogenesis of IgA nephropathy.

Studies of the properties of immune complexes (IC) in the circulation, urine, and mesangium of IgA nephropathy (IgAN) patients have provided data relevant to the pathogenesis of this disease. IC contain predominantly polymeric IgA1 molecules which are deficient in galactose (Gal) residues on O-linked glycan chains in the hinge region (HR) of their heavy (H) chains. As a result of this aberrancy, a novel antigenic determinant(s) involving N-acetylgalactosamine (GalNAc) and perhaps sialic acid (SA) of O-linked glycans is generated and recognized by naturally occurring GalNAc-specific antibodies. Thus, IC in IgAN consist of Gal-deficient IgA1 molecules as an antigen, and GalNAc-specific IgG and/or IgA1 as an antibody. IgG antibodies to Gal-deficient IgA1 are probably induced by cross-reactive microbial antigens; they are present at variable levels not only in humans with or without IgAN but also in many phylogenetically diverse vertebrate species. Incubation of human mesangial cells with IC from sera of IgAN patients indicated that stimulation of cellular proliferative activity was restricted to the large (>800 kDa) complexes. These findings suggest that experimental approaches that prevent the formation of large Gal-deficient IgA1-IgG IC may be applied ultimately in an immunologically mediated therapy.

[Treatment of IgA nephropathy]. / Lécba IgA nefropatie.

IgA nephropathy is the most common cause of chronic renal failure among primary glomerulonephritides. During the last decade, there was a remarkable progress in understanding its pathogenesis. A number of therapeutic trials has been published that shed light on its treatment. ACEI and AT1R antagonists (sartans) or their combination represent the cornerstone of therapy of IgA nephropathy. However, this treatment is not given to patients having optimal blood pressure, normal glomerular filtration rate, proteinuria less than 0.3 g/24 h, mild abnormalities in renal biopsy, and stationary course of the disease. The medication is administered in a maximal tolerated dose to patients with active, progressing disease. ACEI and AT1R antagonists are also drugs of the first choice in patients with proteinuric IgA nephropathy. However, if proteinuria does not decrease significantly within 3 months from the beginning of this treatment, administration of glucocorticosteroids is recommended. On the basis of prospective, controlled clinical trials and metaanalyses of other therapeutic studies, it has been concluded that glucocorticosteroids decrease proteinuria and slow down the decline of renal function. A complete remission of proteinuria is the aim of the treatment. The effectiveness of cyclophosphamide in active forms of IgA nephropathy, described in some studies, was not confirmed by metaanalyses. Nevertheless, cyclophosphamide may be effective in some patients with rapidly deteriorating renal function and active morphological findings with cellular extracapillary proliferation.

Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies.

Circulating immune complexes (CICs) isolated from sera of patients with IgA nephropathy (IgAN) consist of undergalactosylated, mostly polymeric, and J chain-containing IgA1 and IgG antibodies specific for N-acetylgalactosamine (GalNAc) residues in O-linked glycans of the hinge region of IgA1 heavy chains. Antibodies with such specificity occur in sera of IgAN patients, and in smaller quantities in patients with non-IgA proliferative glomerulonephritis and in healthy controls; they are present mainly in the IgG (predominantly IgG2 subclass), and less frequently in the IgA1 isotype. Their specificity for GalNAc was determined by reactivity with IgA1 myeloma proteins with enzymatically removed N-acetylneuraminic acid (NeuNAc) and galactose (Gal); removal of the O-linked glycans of IgA1 resulted in significantly decreased reactivity. Furthermore, IgA2 proteins that lack the hinge region with O-linked glycans but are otherwise structurally similar to IgA1 did not react with IgG or IgA1 antibodies. The re-formation of isolated and acid-dissociated CICs was inhibited more effectively by IgA1 lacking NeuNAc and Gal than by intact IgA1. Immobilized GalNAc and asialo-ovine submaxillary mucin (rich in O-linked glycans) were also effective inhibitors. Our results suggest that the deficiency of Gal in the hinge region of IgA1 molecules results in the generation of antigenic determinants containing GalNAc residues that are recognized by naturally occurring IgG and IgA1 antibodies.

Inhibitors of cyclic nucleotide phosphodiesterase isozymes type-III and type-IV suppress mitogenesis of rat mesangial cells.

We studied interactions between the mitogen-activated protein kinase (MAPK) signalling pathway and cAMP-protein kinase (PKA) signaling pathway in regulation of mitogenesis of mesangial cells (MC) determined by [3H]thymidine incorporation, with or without added EGF. Forskolin or dibutyryl cAMP strongly (by 60-70%) inhibited [3H]thymidine incorporation into MC. Cilostamide, lixazinone or cilostazol selective inhibitors of cAMP-phosphodiesterase (PDE) isozyme PDE-III, inhibited mitogenesis to similar extent as forskolin and DBcAMP and activated in situ PKA, but without detectable increase in cAMP levels. Cilostamide and cilostazol were more than three times more effective at inhibiting mesangial mitogenesis than rolipram and denbufylline, inhibitors of isozyme PDE-IV, even though PDE-IV was two times more abundant in MC than was PDE-III. On the other hand, when incubated with forskolin, rolipram-enhanced cAMP accumulation was far greater (10-100x) than with cilostamide. EGF increased MAPK activity (+300%); PDE isozyme inhibitors which suppressed mitogenesis also inhibited MAPK. PDE isozyme inhibitors also suppressed PDGF-stimulated MC proliferation. We conclude that cAMP inhibits the mitogen-dependent MAPK-signaling pathway probably by decreasing the activity of Raf-1 due to PKA-catalyzed phosphorylation. Further, we surmise that minor increase in the cAMP pool metabolized by PDE-III is intimately related to regulation of mesangial proliferation. Thus, PDE isozyme inhibitors have the potential to suppress MC proliferation by a focused effect upon signaling pathways.

Patients with IgA nephropathy have altered levels of immunomodulatory C19 steroids. Glucocorticoid therapy with addition of adrenal androgens may be the choice.

Glucocorticoid (GC) therapy is one of the methods of choices for treatment of autoimmune diseases (ADs). In addition, adrenal androgens are known as immunoprotective GC-antagonists. Adrenal steroids preferentially influence the Th1-components over the Th2 ones. We investigated steroid metabolome (using gas chromatography-mass spectrometry) in healthy controls (H), GC-untreated patients with ADs different from IgA nephropathy (U), GC-treated patients with ADs different from IgA nephropathy (T) and in patients with IgA nephropathy (IgAN), which were monitored on the beginning (N0), after one week (N1) and after one month (N2) of prednisolone therapy (60 mg of prednisolone/day/m(2) of body surface). Between-group differences were assessed by one-way ANOVA, while the changes during the therapy were evaluated by repeated measures ANOVA. The ANOVA testing was followed by Duncan's multiple comparisons. IgAN patients and patients with other ADs exhibited lack of adrenal androgens due to attenuated activity of adrenal zona reticularis (ZR). Androgen levels including their 7alpha-, 7beta-, and 16alpha-hydroxy-metabolites were further restrained by GC-therapy. Based on these results and data from the literature, we addressed the question, whether a combination of GCs with delta(5)-steroids or their more stable synthetic derivatives may be optimal for the treatment of antibodies-mediated ADs.

Initial single-center experience with sirolimus after lung transplantation.

BACKGROUND: Standard immunosuppression after lung transplantation includes calcineurin inhibitors, mycophenolate mofetil, and steroids. Long-term survivors of lung transplantation are often confronted with chronic kidney disease, by definition related to the intake of calcineurin inhibitors. Sirolimus has been increasingly proposed as an alternative immunosuppressive agent due to its absence of nephrotoxicity, which could be used in selected patients. METHODS: We prospectively administered sirolimus as an alternative to calcineurin inhibitors in 10 lung transplantation recipients with persistent drug nephrotoxicity. They were switched from tacrolimus to sirolimus. Four patients also had bronchiolitis obliterans syndrome. The conversion scheme consisted of an immediate stop of tacrolimus and an 6 to 8-mg loading dose of sirolimus, followed by 4 mg/d. After 5 days, the sirolimus dose was adjusted to maintain trough levels between 12 and 18 ng/mL or 6 and 12 ng/mL for combined sirolimus and tacrolimus. Patients were monitored for renal and graft function as well as clinical status. RESULTS: A significant decrease in creatinine was observed after 1 week of treatment (P = .011). Azotemia decreased after 1 month, remaining stable (P < .01). Pulmonary function tests did not show significant modification from before sirolimus, inception in patients with or without bronchiolitis obliterans syndrome. There were seven infections. One patient died of complications related to bronchiolitis obliterans. CONCLUSION: Sirolimus was a useful alternative immunosuppressant, allowing significant tacrolimus withdrawal in transplant recipients with renal impairment. Sirolimus administration allowed recovery of renal function with low morbidity; it was useful for rescue of chronic renal impairment after lung transplantation.

[Immunoglobulin A and renal diseases]. / Imunoglobulin A a choroby ledvin.

Immunoglobulin A (IgA) is a dominant immunoglobulin of the mucosal surfaces, but it is also present in plasma. In men and in hominoid primates it occurs in two subclasses: IgA1 and IgA2. Circulating IgA is mostly IgA1 monomer, secretory IgA is mostly dimer or tetramer with varying content of IgA1 and IgA2 on individual mucosal surfaces. Its main physiological function is a defence of the mucosal surfaces against infection. It binds either specifically to bacterial antigens or through its O-linked glycosidic chains, it binds to the lectins of bacterial cells and thus protects mucosal surfaces against bacterial adhesion and infection. On each of its heavy chain, IgA1 has at least two N-glycosidically bound oligosaccharides and 3 to 5 O-linked side-chains. The occurrence of O-glycosidically bound glycans on other circulating immunoglobulins is rare. An aberrant composition of these glycans may be an antigenic determinant for naturally occurring circulating antibodies. The resulting IgA-containing immune complexes, which are deposited in the glomeruli, may be the cause of IgA nephropathy. IgA glomerular deposits are also frequently present in many other primary and systemic glomerulonephritides.

[Chronic nephropathies and disorders of renal function--is it sufficiently diagnosed in patients hospitalised on department of internal medicine and cardiology?]. / Jsou chronická onemocnení ledvin a poruchy ledvinné funkce na standardním luzku interních oboru dostatecne diagnostikovány?

We have found out that nephropathies and renal dysfunctions are diagnosed insufficiently. At the same time, it has been observed that patients are sent to nephrology out-patient clinics too late. The aim of our study was to identify how nephropathy and renal dysfunction are diagnosed and how these diagnoses are recorded in diagnostic summary of hospital discharge report in patients hospitalized in department of internal medicine and cardiology of a big teaching hospital. Also, we studied the incidence of risk diseases (arterial hypertension and diabetes mellitus) and serious cardiovascular complications in individual stages of renal dysfunction. We analysed 325 medical records of patients hospitalized and discharged in the course of one month. Renal dysfunction was classified according to Kidney Disease Outcomes Quality Initiative. Glomerulal filtration rate was calculated via simplified Levey's formula. Nephropathy and renal dysfunction were diagnosed, and properly recorded in diagnostic summary, only in 5 % of patients in the Stage I of renal dysfunction (Stage II = 2%, Stage III = 28%, Stage IV = 88% and Stage V = 88%). The incidence of risk diseases and cardiovascular complications increased linearly with progression of renal insufficiency. The results of our study prove that nephropathy and renal dysfunction are diagnosed insufficiently, particularly in early stages when it is still possible to use targeted therapy and early control of specific complications of renal insufficiency.

Ultrastructural immunohistochemistry of glomerulonephritis in needle biopsy.

In two patients with glomerulonephritis (GN) IgG and C 3 were visualized in ultrastructure by means of HRP-conjugated antisera. The first patient had an acute postinfectious extra-intracapillary GN lasting for about two months with granular fluorescence of anti-IgG, -C 3, and -C 1q. Electron microscopy revealed widespread endothelial defects, a well-pronounced polymorphonuclear stasis, and typical perimembranous "humps". These deposits reacted with HRP-anti-C 3 but the ultrastructural proof of IgG was negative. A weak and sporadic reaction of both these conjugates was seen in the swollen mesangial matrix while intraluminal plugs of coagulated plasma and extracapillary exudates yielded a dense coarse reaction product. In the second patient (allograft, three years after transplantation) the membranous and proliferative probably recurrent GN with nephrotic syndrome showed massive perimembranous deposits in the late involution stage. Granular fluorescence of the main Ig classes and of C 3 was sporadic or absent. In the ultrastructural immunoenzyme assay, too, the residues of deposits failed to react with HRP-anti-IgG or -C 3 and the mesangial matrix harboured only sporadic foci of faint positivity; however, dense product was again seen in capillary plasmatic "microthrombi". The discrepancy between immunofluorescence microscopy and immunoenzyme histochemistry, noted also by others in experimental glomerulopathies, may reflect the instability and dynamic properties of immune deposits with an early loss of antibody reactivity and a more protracted though not persistent local activation of complement. In light microscopy, fluorescent granules may correspond not only to the sites of immune deposition but also to accidental intracapillary plasma precipitates.

Experimental ablation nephropathy. Fine structure, morphometry, cell membrane epitopes, glomerular polyanion and effect of subsequent transplantation.

The subtotal (5/6) nephrectomy performed in 23 adult female rats induced severe hypertrophy of residual parenchyma with interstitial fibrosis, tubular dilatation, and focal and segmental glomerulosclerosis (FSG). This ablation nephropathy (AbN) caused proteinuria, progressive renal failure, and hypertension. The extent of FSG was assessed by semiquantitative scoring. The ultrastructure revealed widespread foot process fusion, many dense cytoplasmic inclusions in podocytes, and degenerative changes or disruption of mesangium with glomerular "microcysts". Numerous granular deposits of rat Ig were seen in the glomeruli but a short praeterminal i.v. load by heat-aggregated human Ig did not alter the morphology of AbN and produced discrete and inconstant glomerular deposits. Similarly an i.v. injection of protamine and heparin generated protamine-heparin complexes seen in various layers of glomerular capillary wall, similar to those found previously in normal rats. AbN displayed a partial irregular depletion of polyanion sites reactive with polyethylenimine in lamina rara externa. A significant increase in both glomerular and interstitial Ia+ cells and a marked predominance of W3/25+ cells in the interstitial infiltrates were documented by immunohistochemistry in the remnant kidneys. Both AbN and FSG could be largely corrected (or prevented?) by subsequent syngeneic renal transplantation (TPL; 6 animals). On the other hand a severe AbN was found in two post-ablation residues after unsuccessful TPL with graft necrosis or sclerosis.--AbN has some analogies to various chronic human nephropathies (e.g. FSG) and may explain their progression to the terminal failure. Degenerative and finally destructive mesangial lesion seems to be of prime importance in AbN.

Protein aggregates in extracorporally perfused rabbit kidneys.

Eighteen rabbit kidneys were perfused ex vivo for 1 h with allogeneic blood, and in 16 a solution of xenogeneic aggregate-free, aggregated or antibody-complexed protein was added to the perfusate 5 min after the start (human immunoglobulins or serum albumin, partly cationized, were used). The kidneys were examined by light and electron microscopy and the human and rabbit immunoglobulin (or albumin) precipitates were detected by direct immunofluorescence and ultrastructural immunohistochemistry. In 13 kidneys the perfusion produced small segmental glomerular endocapillary aggregates of platelets, leukocytes, and granular precipitates reactive with both anti-rabbit and anti-human antibodies. No typical deposits were seen in mesangium or in periphery of glomerular capillaries but rabbit Ig penetrated to the inter- and subepithelial spaces of proximal convoluted tubules. Three kidneys perfused by cationized aggregated human Ig (or by cationized albumin-antialbumin complexes) exhibited a destructive lesion with rapid breakdown of blood flow and massive global endocapillary plugs of similar ultrastructure but with focal endothelial sloughing. Pericapillary granular precipitates of human and rabbit Ig were seen in these kidneys. When the blood with cationized Ig aggregates was used for perfusion of two further kidneys extensive endocapillary aggregates with endothelial damage reappeared but the extracapillary penetration and precipitation were lacking and the blood flow largely improved. Membrane polyanion of podocytes stained by colloidal iron was preserved even in close proximity of cationized complex precipitates. Thus, in the ex-vivo perfusion model the preformed neutral aggregates did not penetrate through the glomerular capillary wall and were not phagocytized by mesangial cells. The cationized aggregates induced rapid circulatory failure with massive platelet clumping and granular pericapillary "humps" ultrastructurally different from the deposits of human and experimental immune complex glomerulonephritis.

Wegener's granulomatosis with bilateral necrotizing scleritis, polyarthritis and renal failure efficiently treated with immunosuppressive therapy.

A case report of a female patient with Wegener's granulomatosis is presented. After an initial involvement of the upper respiratory tract in the form of a sinusitis, there followed a severe necrotizing bilateral scleritis necessitating the enucleation of the left eye ball. Renal involvement developed as late as 24 months after the onset of the disease and led to renal failure within three months. Throughout the duration of her disease, the patient had joint symptoms in the form of episodes of migratory nondeforming polyarthritis. The administration of corticosteroids alone in daily doses up to 60 mg prednisone failed to control the progression of the disease, while immunosuppressive therapy with cyclophosphamide combined with methylprednisolone pulse therapy and haemodialysis resulted in a marked improvement of renal function and in the subsidence of the ocular and articular symptoms.

Comparison of three dosage regimens of ciprofloxacin in urinary tract infections.

Fifty-four patients with complicated UTI were administered ciprofloxacin in doses of 500 mg (30 subjects) and 250 mg (24 subjects) at 12-hour intervals. While a positive effect was noted in 96-100% upon termination of therapy, the effect was still present 3 weeks later in 90% of the high-dose, but only in 71% of the low-dose group. In 23 patients with uncomplicated UTI, a positive effect of the three-day therapy with 100 mg of ciprofloxacin at 12-hour intervals was observed in 91% of subjects. Intolerance to the agent was found in one case only. Development of resistance to ciprofloxacin was not observed.

Effect of methylprednisolone therapy on lipoprotein metabolism in human nephrotic syndrome.

Changes in the lipoprotein metabolism of 15 patients with nephrotic syndrome concomitant with various types of the underlying renal disease after methylprednisolone therapy were investigated. Following methylprednisolone therapy, nephrotic syndrome remission was achieved only in three patients with minimal change disease. In these patients, total cholesterol (TC) and free cholesterol (FC) decreased and an increase in HDL-C and the HDL-C/TC ratio was found. In the remaining 12 patients, while marked proteinuria persisted after therapy, a significant increase in HDL-C (from 1.38 to 1.83 mmol/l) was noted with no significant changes in TC, FC and TG. Our results suggest that methylprednisolone may affect lipoprotein metabolism without necessarily exerting a favourable effect on the course of kidney disease.

Defect in cholesterol esterification associated with renal diseases.

Changes in lipidaemia and in cholesterol esterification rate were investigated in 65 patients with chronic mesangial glomerulonephritis (GN), and in 26 patients with polycystic kidneys (PL), as well as in age- and sex-matched control groups. As compared to the controls, a slightly significant increase in cholesterol and triglyceride concentrations was found only for the GN group, whereas the rate of cholesterol esterification showed a highly significant reduction in both groups of diseased subjects. The average values of molar esterification rate (MER) were, respectively, 75.4 and 61.6 mumol . l-1 . h-1 for the GN and PL groups, the respective control values being 96.9 and 91.1. Fractional esterification rate (FER) reflecting the rate of cholesterol exchange between blood and tissues fell in the same two groups of patients to 4.38 and 4.40% . h-1, respectively (controls 6.93 and 6.17). Both the changes in cholesterol esterification rates and a relative increase in the ratio of unesterified to esterified cholesterol were found in patients with low as well as normal glomerular filtration rates.

Changes in cyclosporine A kinetics after experimental reduction of renal parenchyma.

Experimental chronic renal insufficiency (produced by 5/6 ablation of renal parenchyma) is associated with changes in the kinetics of oral (intragastric) cyclosporine A (CyA). Compared with animals with intact renal parenchyma, significantly lower levels of CyA are reached under these conditions. The factors responsible for reduced CyA availability under these conditions have not yet been identified.