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.

[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.

[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.

[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.

[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.

[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.

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.

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.

[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.

[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.

[Analysis and adjustment of acid-base disturbances according to the Stewart-Fencl principle]. / Analýza a korekce poruch acidobazické rovnováhy na základe Stewartova-Fenclova principu.

In 1983, P. J. Stewart proposed a new approach for evaluation of acid-base balance of body fluids. He defined three independent variables responsible for hydrogen ion concentration in body fluids: 1. the partial pressure of carbon dioxide (pCO2); 2. strong ion difference, SID, i.e. the difference between the sums of all the strong (fully dissociated, chemically nonreacting) cations and sums of the strong anions; 3. the total concentration of all the non-volatile weak acids (mainly albumin) designated as [Atot]. On the basis of this theory, V. Fencl invented a new classification of clinical acid-base disturbances. Respiratory acidosis and alkalosis result from abnormalities of pCO2. The classifications of the respiratory disturbances of ABR is identical as in the conventional viewing which is based on the dissociation equation of carbonic acid. Metabolic acidoses or alkaloses result from derangements of the SID and/or [Atot]. The change of SID value is a consequence of either dehydration (alkalosis) or hyperhydration (acidosis). Other mechanisms of SID deviation are either changes of serum chloride concentration (an increase causes acidosis, a decrease causes alkalosis) or an increase of concentrations of substances not routinely measured (ketones, lactate, exogenous acids). [Atot] value is determined mainly by the serum albumin concentration (alkalosis in hypoalbuminemia, acidosis in hyperproteinemia). The Stewart-Fencl approach to acid-base balance enables to understand and predict what happens to hydrogen ions in body fluids and to control the pH abnormalities quantitatively.

[IgA nephropathy. Use of modern laboratory methods and renal biopsy for diagnosis]. / IgA nefropatie. Uzití moderních laboratorních metod a biopsie ledviny v diagnostice.

IgA nephropathy is the most frequent primary glomerulonephritis worldwide. At its onset, the most common laboratory sign is isolated haematuria often accompanied with mild proteinuria (up to 1.5 g/24 h). The disease displays a progressive course with end-stage renal disease occurring in up to half of patients 20 years after onset. Diagnosis is established by immunofluorescent microscopy of a renal biopsy specimen. Discoveries in the past decade on the pathogenesis of IgA nephropathy together with complex evaluation of its clinical presentation enable to establish diagnosis with a satisfactory degree of probability even without biopsy. IgA nephropathy patients display increased or borderline serum IgA levels; increased serum levels of IgA fraction with degalactosylated O-linked side sugar chains; increased serum levels of anti-N-acetylgalactosamine antibodies; increased levels of circulating immune complexes composed of IgA1 complexed with IgG or IgA1; increased serum levels of circulating complexes composed of IgA and fibronectin; and frequent occurrence of the rheumatoid IgA factor. Clinical use of these still generally unavailable methods would reduce the renal biopsy indication in patients with isolated or predominant haematuria.

[IgA nephropathy. Significance of immunoglobulin A glycosylation in pathogenesis and clinical presentation]. / IgA nefropatie. Význam glykozylace imunoglobulin A pro patogenezi a její klinický obraz.

Human immunoglobulin A is represented by two structurally and functionally distinct subclasses: IgA1 and IgA2. IgA1, which is almost exclusively present in the mesangial deposits in IgA nephropathy patients, contains in its hinge region three to five O-lined carbohydrate chains. A fraction of IgA1 molecules in the circulation of IgA nephropathy patients exhibits aberrant glycosylation. As a result of changes in glycosylation, the neoepitopes represented by glycans are exposed and recognized by naturally occurring antibodies with antiglycan specifciities, and immune complexes are generated. The deposits of these immune complexes in the glomerular mesangia elicit inflammatory response known as IgA nephropathy. Epidemiological studies have shown that dominant hematuria, either isolated or combined with mild proteinuria, is the most frequent urinary syndrome in glomerulonephritis. The morphologic finding of this syndrome is most frequently IgA nephropathy. Originally considered a benign disease, IgA nephropathy is now recognized as a frequent cause of chronic renal failure. The progression is signalized by increasing proteinuria and hypertension. Therefore, a control of blood pressure and lowering of proteinuria remain the corner-stones of the treatment. Angiotensin converting enzyme inhibitors and AT1 blockers may lower both blood pressure and proteinuria and are now increasingly promoted even for treatment of normotensive patients. Steroids are administered to patients with severe proteinuria. High-doses of fish oil seem to slow down the rate of renal failure.

[Postural trauma and rhabdomyolosis causing acute renal failure]. / Pozicní trauma s rabdomyolýzou a následným akutním renálním selháním.

Rhabdomyolysis (damage of the muscles of various origin) leads to the efflux of the intracellular fluids in the circulation. The common complication of this status is the renal failure. The early diagnosis and the proper treatment makes the fall of renal function reversible. That is why the possibility of the rhabdomyolysis must be consider. The case report describes the development of renal failure in young, previously healthy men, followed by trauma mechanism after drug and alcohol abuse.

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.

[Immunohistochemistry of a biopsy of an allotransplanted kidney]. / Imunohistochemie biopsií alotransplantované ledviny.

BACKGROUND: Cellular rejection infiltration of the interstitium is the basic histological finding in biopsies of transplanted kidneys, and leukostasis in the muscular arteries and glomeruli is an important sign of exacerbating rejection. For better understanding and more accurate interpretation the authors used immunohistochemistry. METHODS AND RESULTS: The authors examined 282 tissue specimens from 208 grafts using the two- or three-step immunoenzyme method with 28 mono- or polyclonal antibodies specific for a series of differentiation and activation leukocytic antigens, adhesion molecules and selected cytokines. In the compact component of the rejection infiltrate CD4+ lymphocytes with expression of CD 45 RA antigen predominated while in the disperse component there were mostly macrophages (CD68, 14, 11b); their number correlated significantly with the parenchymatous damage, similarly as intraarterial and glomerular accumulation. The disperse infiltrate and adherent cells expressed CD45 RO (rarely CD25) and integrin molecules of the series CD11 and CD49 CD57+ lymphocytes penetrated into the tubules but did not accumulate in the blood vessels. As to adhesive molecules of the "Ig superfamily", CD106 (VCAM-1) was more important than CD54 (ICAM-1) and its arterial and mesangial expression correlated with the rejection damage. Evidence of cytokines (IL1, IL2, TNF alpha, beta) did provide neither unequivocal results nor correlations. CONCLUSIONS: Immunohistochemistry improves considerably the accuracy of bioptic evaluation of rejection nephropathy and some antigens (e.g., CD68, CD14, CD45 RO., CD57, CD106) are suitable for diagnostic practice. With their aid it is easier to evaluate the activity of rejection, assess the probability of vascular lesions in specimens without affected vessels and detect more sensitively intravascular stasis and adhesion of leukocytes.

Inhibitors of cyclic nucleotide phosphodiesterase isozymes block renal tubular cell proliferation induced by folic acid.

In previous studies we observed that inhibition of cyclic 3',5'-nucleotide phosphodiesterase (PDE) isozymes, namely isozyme PDE3, suppresses proliferation of rat renal glomerular mesangial cells in vitro and in vivo. To determine whether activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway coupled to specific PDE isozymes modulates accelerated proliferation of renal epithelial cells, we investigated the effect of selective PDE isozyme inhibition on renal epithelial cell proliferation induced in rats by injection of folic acid (FA). In extracts from suspensions of renal cortical tubules, cAMP was metabolized predominantly by isozyme PDE4; activity of PDE3 was about three times lower. The increase in proliferative activity of renal cortical tissue from FA-injected rats, evaluated by immunostaining with Mib-1 antibody, was limited to tubular epithelial cells. Administration of the PDE3 inhibitors cilostazol or cilostamide together with the PDE4 inhibitor rolipram blocked mitogenic synthesis of DNA, as determined by (3H)-thymidine incorporation into renal cortical DNA, in FA-treated rats. FA injection caused an increase of more than 10-fold in proliferating cell nuclear antigen (PCNA) in renal cortical tissue; administration of the potent PDE3 inhibitor lixazinone or, to a lesser degree, cilostazol suppressed these high PCNA levels, whereas rolipram alone had no effect. The results indicate that FA-stimulated in vivo proliferation of renal tubular epithelial cells is down-regulated by activation of a cAMP-PKA signaling pathway linked to PDE3 isozymes. These observations are consistent with the notion that negative crosstalk between cAMP signaling and mitogen-stimulated signaling pathways regulates mitogenesis of renal cells of different terminal differentiation, including tubular epithelial cells.

Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in complexes with IgG.

IgA1 proteins from sera of patients with IgA nephropathy (IgAN) are galactosylated to a lesser degree than those from healthy controls. The increased reactivity of intact or de-sialylated serum IgA1 with N-acetylgalactosamine (GalNAc)-specific lectins, Helix aspersa (HAA) and Caragana arborescens (CAA) and de-sialylated IgA1 with Helix pomatia (HPA) and Bauhinia purpurea (BPA) indicated that the Gal deficiency is in glycans located in the hinge region of IgA1 molecules. De-sialylated IgA from sera of 81 IgAN patients bound biotin-labeled lectin HAA more effectively than did de-sialylated IgA from 56 healthy controls (P < 0.0001). Similar results were observed for 67 IgAN patients and 52 controls with second lectin, CAA (P < 0.001). The binding patterns for 9 patients with mesangial proliferative glomerulonephritis of non-IgA origin were similar to those for controls. Incompletely galactosylated IgA1 capable of binding GalNAc-specific lectins was detected in complexes with IgG as demonstrated by ELISA, size-exclusion chromatography and sucrose gradient ultracentrifugation. The formation of IgA1-IgG complexes may affect the serum level of IgA1 by reducing the rate of its elimination and catabolic degradation by the liver.