Protective Effect of PACAP on Ischemia/Reperfusion-Induced Kidney Injury of Male and Female Rats: Gender Differences.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts general cytoprotective effects, including protection in different kidney disorders. The aim of our study was to investigate the ischemia/reperfusion-induced kidney injury of male and female rats to confirm the protective effects of PACAP in the kidney and to reveal possible gender differences.Male and female Wistar rats underwent unilateral renal artery clamping followed by 24-h, 48-h, or 14-day reperfusion. PACAP was administered intravenously before arterial clamping in half of the rats. Tubular damage, cytokine expression pattern, oxidative stress marker, antioxidative status and signaling pathways were evaluated using histology, immunohistology, cytokine array, PCR, and Western blot. Tubular damage was significantly less severe in the PACAP-treated male and female rats compared to controls. Results of female animals were significantly better in both treated and untreated groups. Cytokine expression, oxidative stress marker and antioxidative status confirmed the histological results. We also revealed that PACAP counteracted the decreased PKA phosphorylation, influenced the expression of BMP2 and BMP4, and increased the expression of the protein Smad1.We conclude that PACAP is protective in ischemia/reperfusion-induced kidney injury in both sexes, but females had markedly less pronounced injury after ischemia/reperfusion, possibly also involving further protective factors, the investigation of which could have future therapeutic value in treating ischemic kidney injuries.

σ1-Receptor Agonism Protects against Renal Ischemia-Reperfusion Injury.

Mechanisms of renal ischemia-reperfusion injury remain unresolved, and effective therapies are lacking. We previously showed that dehydroepiandrosterone protects against renal ischemia-reperfusion injury in male rats. Here, we investigated the potential role of σ1-receptor activation in mediating this protection. In rats, pretreatment with either dehydroepiandrosterone or fluvoxamine, a high-affinity σ1-receptor agonist, improved survival, renal function and structure, and the inflammatory response after sublethal renal ischemia-reperfusion injury. In human proximal tubular epithelial cells, stimulation by fluvoxamine or oxidative stress caused the σ1-receptor to translocate from the endoplasmic reticulum to the cytosol and nucleus. Fluvoxamine stimulation in these cells also activated nitric oxide production that was blocked by σ1-receptor knockdown or Akt inhibition. Similarly, in the postischemic rat kidney, σ1-receptor activation by fluvoxamine triggered the Akt-nitric oxide synthase signaling pathway, resulting in time- and isoform-specific endothelial and neuronal nitric oxide synthase activation and nitric oxide production. Concurrently, intravital two-photon imaging revealed prompt peritubular vasodilation after fluvoxamine treatment, which was blocked by the σ1-receptor antagonist or various nitric oxide synthase blockers. In conclusion, in this rat model of ischemia-reperfusion injury, σ1-receptor agonists improved postischemic survival and renal function via activation of Akt-mediated nitric oxide signaling in the kidney. Thus, σ1-receptor activation might provide a therapeutic option for renoprotective therapy.

Modeling long-term diabetes and related complications in rats.

INTRODUCTION: Accurate preclinical modeling of diabetic complications such as retinopathy, nephropathy and neuropathy is crucial to enable the development of novel preventative therapies. The aims of this study were to establish a model of long-term diabetes with sustained medium scale hyperglycemia and characterize the pathological changes detectable after 4months, with particular respect to dependence on the degree of hyperglycemia. METHODS: Streptozotocin-induced diabetic CFY rats were subjected to four different insulin substitution protocols to achieve different levels of glycemic control (Diabetic 1-4 groups). Eyes were investigated by ophthalmoscopy, kidney function by urine analysis, and neuropathy by functional tests. Retinal and renal morphological evaluations were performed by histology, immuno-histochemistry and electron microscopy. RESULTS: Rats of the Diabetic 3 group showed massive hyperglycemia-dependent anterior segment neovascularization, enhanced total retinal score and retinal apoptotic cell number, degeneration of dopaminergic amacrine cells, increased glomerular PAS-positivity, altered excreted total protein/creatinine ratio and cold allodynia, parallel with medium scale hyperglycemia (blood glucose level between 22 and 25mmol/L) and satisfying state of health. DISCUSSION: We established a treatment protocol in rats enabling complex investigation of diabetic retinopathy, nephropathy and neuropathy on a long-term period. Clearly hyperglycemic dependent parameters of these complications serve as good outcome measures for preclinical trials. Our results provide a useful basis for designing studies for testing preventative treatments as well as other translational medical research in this field.

Effect of tonsillectomy and its timing on renal outcomes in Caucasian IgA nephropathy patients.

PURPOSE: The role of tonsillectomy in the treatment of IgA nephropathy in Caucasian patients is controversial. METHODS: A retrospective cohort study was conducted in 264 patients with biopsy-proven primary IgA nephropathy to examine the association between tonsillectomy and long-term renal survival, defined as the incidence of estimated glomerular filtration rates (eGFRs) of ≤30 ml/min/1.73 m(2) or end-stage renal disease (the composite of initiation of dialysis treatment or renal transplantation). The association of tonsillectomy with renal end-points was examined using the Kaplan-Meier method and Cox models. RESULTS: One-hundred and sixty-six patients did not undergo tonsillectomy (Group I, follow-up 130 ± 101 months) and 98 patients underwent tonsillectomy (Group II, follow-up 170 ± 124 months). The mean renal survival time was significantly longer for both end-points between those patients who underwent tonsillectomy (Group II) versus patients without tonsillectomy (Group I) (p < 0.001 and p = 0.005). The mean renal survival time was significantly longer for both end-points between those patients who had macrohaematuric episodes versus patients who had no macrohaematuric episodes (p = 0.035 and p = 0.019). Tonsillectomy, baseline eGFR and 24-h proteinuria were independent risk factors for both renal end-points. CONCLUSION: Tonsillectomy may delay the progression of IgA nephropathy mainly in IgA nephropathy patients with macrohaematuria. Prospective investigation of the protective role of tonsillectomy in Caucasian patients is needed.

Molecular mechanisms underlying the Nephroprotective effects of PACAP in diabetes.

Diabetic nephropathy is the leading cause of end-stage renal failure and accounts for 30-40 % of patients entering renal transplant programmes. The nephroprotective effects of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38) against diabetes have been shown previously, but the molecular mechanisms responsible for these effects remain unknown. In the present study, we showed that PACAP treatment counteracted the diabetes-induced increase in the level of the proapoptotic pp38MAPK and cleaved caspase-3 and also decreased the p60 subunit of NFκB. The examined antiapoptotic factors, including pAkt and pERK1/2, showed a slight increase in the diabetic kidneys, while PACAP treatment resulted in a notable elevation of these proteins. PCR and Western blot revealed the downregulation of fibrotic markers, like collagen IV and TGF-ß1 in the kidney. PACAP treatment resulted in increased expression of the antioxidant glutathione. We conclude that the nephroprotective effect of PACAP in diabetes is, at least partly, due to its antiapoptotic, antifibrotic and antioxidative effect in addition to the previously described antiinflammatory effect.

PARP inhibition attenuates acute kidney allograft rejection by suppressing cell death pathways and activating PI-3K-Akt cascade.

BACKGROUND: Novel immunosuppressive therapy facilitates long term allograft survival, but acute tubular necrosis and ischemia-reperfusion during transplantation can compromise allograft function. These processes are related to oxidative stress which activates poly- (ADP-ribose) polymerase (PARP) contributing to the activation of cell death pathways. Here we raised the possibility that PARP inhibition curbs cell death pathways and shifts kinase signaling to improved graft survival. METHODS FINDINGS: In an acute rat kidney rejection model, we provided evidence that the PARP inhibitor 4-hydroxy-quinazoline (4OHQ) attenuates rejection processes initiated oxidative/nitrosative stress, nuclear poly-ADP-ribosylation and the disintegration of the tubulo-interstitial structures. The PARP inhibitor attenuated rejection processes induced pro-apoptotic pathways by increasing Bcl-2/Bax ratio and suppressing pro-apoptotic t-Bid levels. In transplanted kidneys, the cell death inducing JNK1/2 is normally activated, but PARP inhibition suppressed this activation with having only modest effects on ERK1/2 and p38 MAP kinases. In untreated transplanted kidneys, no significant alterations were detected in the cytoprotective PI-3K-Akt pathway, but the PARP inhibitor significantly activated Akt (by S473 phosphorylation) and suppressed GSK-3ß, as well as activated acute NF-kappaB activation contributing to graft protection. CONCLUSION: These data show the protective role of PARP inhibition on graft survival by attenuating poly-ADP-ribosylation, oxidative stress, suppressing pro-apoptotic and increasing anti-apoptotic protein level, and by shifting MAP kinases and PI-3-K-Akt pathways to cytoprotective direction. Thus, addition of PARP inhibitors to standard immunosuppressive therapies during kidney transplantation may provide increased protection to prolong graft survival.

Smoking as the potential link between Kimmelstiel-Wilson lesion and non-diabetic nodular glomerulosclerosis in male patients - a single center retrospective study.

BACKGROUND: The histological pattern of nodular glomerulosclerosis (NGS) can be found both in diabetic nephropathy (Kimmelstiel-Wilson (KW) lesion) and non-diabetic nodular glomerulosclerosis (non-diab NGS). Chronic smoking is considered to be a potential cause of non-diab NGS, but the prevalence of smokers in KW is unknown. METHODS: In a retrospective analysis, native renal biopsy specimens (n = 644, 2001 - 2011) were evaluated and male patients' characteristics, including smoking habits, were assessed within three groups: diabetic patients with KW (n = 15), diabetic patients with other classes of diabetic nephropathy (non-KW; n = 46), and patients with non-diab NGS (n = 7). RESULTS: The majority of patients in the KW and non-diab NGS groups (13/15 = 87%, 7/7 = 100%, respectively; p = 1.0 vs. KW) were smokers, unlike the non-KW group (16/46 = 35%; p = 0.001 vs. KW). Cigarette pack-years showed a similar pattern (KW: 15 (6 - 30), non-KW: 0 (0 - 21), non-diab NGS: 30 (16 - 33); p = 0.010 non-KW vs. KW, p = 0.008 non-KW vs. non-diab NGS). Other known factors responsible for the worsening of non-KW or the development of non-diab NGS did not differ in the groups (age, body mass index, duration of diabetes mellitus, HbA1c, prevalence of hypertension, duration of hypertension, serum cholesterol, triglyceride, estimated glomerular filtration rate, and renin-angiotensin-aldosteron system-blocker treatment). CONCLUSIONS: We propose that chronic cigarette smoking could play a pivotal role in the development of KW lesions.

Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats.

Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers.

Histological diagnosis determines complications of percutaneous renal biopsy: a single-center experience in 353 patients.

BACKGROUND: We studied the connection between complication occurrence related to renal biopsies and histological diagnoses of the biopsy specimen. We also analyzed the distribution of diagnoses in our population. METHODS: We retrospectively studied 353 patients undergoing renal biopsy at the same center. Biopsies were performed after marking the site of puncture by ultrasound imaging. Connection of complications with diagnoses and clinical parameters was evaluated. RESULTS: Complication rate was 44.5% in our study. There was a significantly lower rate of complications in patients with diabetic nephropathy (likelihood ratio, LR = 0.44) or acute tubular necrosis (LR = 0.38), while patients with thin basement membrane syndrome had a more than 6-fold higher risk for development of intrarenal hemorrhage than others. Patients with vasculitis (LR = 2.88) and acute interstitial nephritis (LR = 3.18) have a more than doubled risk for arteriovenous shunts, while in patients with severe arteriosclerosis the prevalence of this complication was lower (LR = 0.46). Arteriovenous shunts developed also at a significantly higher rate in patients with rapidly progressive glomerulonephritis. CONCLUSION: Patients with thin basement membrane syndrome, vasculitis, rapidly progressive glomerulonephritis or acute interstitial nephritis should be observed more carefully after renal biopsy due to the significantly higher risk for certain complications.

[Therapy in IgA nephropathy--when and how to do it]. / Az IgA-nephropathia terápiája. Mikor és hogyan kezeljünk?

IgA nephropathy is the most common primary glomerulonephritis worldwide. The clinical spectrum covers a wide range of features from minor urinary abnormalities (asymptomatic hematuria and mild proteinuria with normal renal function) to acute and chronic renal insufficiency. Ideally, the goal of treatment would be to correct any defects in IgA1 glycosylation and to modify mesangial deposition or removal of IgA1 deposits. There are only a few randomized controlled trials in IgA nephropathy; for this reason most treatment options are largely based on expert opinion. Authors discuss therapeutic options of different clinical pictures and the optimized renoprotective treatment of all IgA nephropathy patients.

Renal involvement in Crohn's disease: granulomatous inflammation in the form of mass lesion.

Extraintestinal manifestations of Crohn's disease (CD) are varied and concentrated mainly to the skin and eye. Urinary tract or renal involvement is extremely rare. Herein we report on a case of renal lesion of a 50-year-old woman with a 15-year history of CD. Abdominal computed tomography scan of the patient identified heterogeneous multinodular mass lesions in the left kidney. Histology proved classic granulomatous inflammatory nodules with multinucleated giant cells, eosinophils, plasma cells, epithelioid cells, and spindle-shaped myofibroblasts in the areas, where the computed tomography scan indicated. After the extensive PubMed search in the literature, this is the first macroscopically documented and histologically proved, mass-like renal involvement in CD. From now on, differential diagnostics of renal mass lesions in CD should include the tumor-like, Crohn's-type granulomatous inflammation as direct kidney manifestation of the disease.

Gender differences in serum and glucocorticoid regulated kinase-1 (SGK-1) expression during renal ischemia/reperfusion injury.

Several studies reported sexual dimorphism in the signaling mechanisms of renal ischemia/reperfusion (I/R). The anti-apoptotic serum and glucocorticoid-regulated kinase-1 (SGK-1) is up-regulated and has a significant protective role in renal I/R. SGK-1 has several target molecules, and inhibition of the inducible nitric oxide synthase (iNOS) transcription is one of its effector mechanisms. The objective of the present study was to examine if there is a gender-specific expression and activation of SGK-1 during renal I/R injury. In vitro, treatment of HK-2 kidney proximal tubular cells with different concentrations of 17-beta estradiol had no effect, whereas testosterone increased SGK-1 abundance in a dose-dependent manner. In vivo, in a rat model of unilateral renal I/R injury, there was a higher SGK-1 expression and phosphorylation in males 2 and 24 h after ischemia paralleled by reduction in the mRNA expression of iNOS compared to females. Deprivation of testosterone by castration of males resulted in decreased SGK-1 protein level at all time-points and reduced phosphorylation 2 and 24 h after reperfusion. Our results suggest that testosterone up-regulates SGK-1 in the kidney contributing to sexual dimorphisms in the cell signalling machinery. The significance of the testosterone-regulated SGK-1 level and activity in the kidney needs further investigations.

Renoprotective effect of erythropoietin in rats subjected to ischemia/reperfusion injury: gender differences.

BACKGROUND: Renal ischemia reperfusion injury induces gender-dependent heat-shock protein 72 expression, which maintains membrane localization of renal Na(+)/K(+)ATPase-α1. The erythropoietin has a protecting effect against ischemia reperfusion injury in various organs. In this study, we investigated whether erythropoietin exerts a beneficial effect against post-ischemic renal injury. Furthermore, we studied the erythropoietin signaling on heat-shock protein 72 and Na(+)/K(+)ATPase-α1 expression and localization. METHODS: In male and female Wistar rats, rHuEPO (1000 IU/bwkg intraperitoneal) or vehicle was administered 24 hours prior to unilateral left renal ischemia reperfusion (50 minutes). Kidneys were subsequently removed at hours 2 or 24 of the reperfusion; sham-operated rats served as controls (C) (n = 8/group). We measured serum erythropoietin, renal function, evaluated histological injury, and observed heat-shock protein 72 as well as Na(+)/K(+)ATPase-α1 protein level and localization. Additional groups were followed for 7-day survival. RESULTS: Erythropoietin treatment was associated with better post-ischemic survival and less impaired renal function in males while diminishing the renal structural damage in both sexes. Endogenous erythropoietin was higher in males and increased in both genders after erythropoietin treatment. The erythropoietin treatment elevated protein levels of heat-shock protein 72 and Na(+)/K(+)ATPase-α1 in 24 hours in males, whereas in females, the already higher expression of heat-shock protein 72 and Na(+)/K(+)ATPase-α1 was not increased. Moreover, erythropoietin prevented ischemia reperfusion induced Na(+)/K(+)ATPase-α1 translocation from the basolaterale membrane in males. CONCLUSION: Erythropoietin diminishes gender difference in the susceptibility to renal post-ischemic injury and reduces post-ischemic structural damage while preserving kidney function, particularly in males. This additional protection may be associated with a heat-shock protein 72-mediated effect on Na(+)/K(+)ATPase-α1 expression and translocation.

Accumulation of renin and imidazolone in peritubular capillary endothelial cells in insulin-resistant hypertensive rats.

BACKGROUND: Peritubular endothelium plays a key role in the development and progression of diabetic and nondiabetic chronic kidney disease. Renal injury in disorders of glucose metabolism may appear as early as in the stage of impaired glucose tolerance (IGT) and is accelerated by hypertension. The aim of our study was to investigate renal histology in rats with hypertension and IGT, with special emphasis on the peritubular endothelium. METHODS: Hypertension and IGT (H/IGT) were provoked in adult male Wistar rats by bilateral administration of methylglyoxal into the ventromedial hypothalamus. Immunohistochemistry with anti-renin and anti-imidazolone antibodies and immunoelectron microscopy with anti-renin antibody were performed. RESULTS: H/IGT rats showed tubulointerstitial fibrosis as well as renin and imidazolone staining in the papillary region. The patterns of immunostaining for renin and imidazolone were similar to that of endothelium. On electron microscopy, peritubular capillary endothelial cells and to a less extent, tubular epithelial cells showed renin positivity. DISCUSSION: Impaired glucose tolerance complicated with hypertension leads to tubulointerstitial fibrosis in rat kidney. Imidazolone deposition and renin production in peritubular capillary endothelial cells may play a role in the development of tubulointerstitial fibrosis.

Evidence of O-linked N-acetylglucosamine in diabetic nephropathy.

AIMS: There is increasing evidence that O-linked N-acetylglucosamine (O-GlcNAc) plays an important role in cell signaling pathways. It has also been reported that increases in O-GlcNAc contribute to the development of diabetes and diabetic complications; however, little is known about O-GlcNAc levels in diabetic nephropathy (DNP). Therefore the goal of this study was to determine whether O-GlcNAc could be detected in human kidney biopsy specimens, and if so to examine whether O-GlcNAc levels were increased in the kidneys of patients with DNP compared to the non-diabetic individuals. MAIN METHODS: Kidney biopsy specimens were obtained from type-2 diabetic patients (n=6) and patients diagnosed with thin basement membrane nephropathy (n=7) were used as non-diabetic controls. O-GlcNAc levels were assessed by immunohistochemistry using the anti-O-GlcNAc antibody CTD110.6. KEY FINDINGS: We show that O-GlcNAc modification of proteins can be detected in the human kidney biopsy specimens. Furthermore, in diabetic patients, we found significantly increased numbers of O-GlcNAc positive cells in the glomeruli and significantly elevated staining in the tubuli (both in the nucleus and in the cytosol). In addition we also observed an intense, granular O-GlcNAc staining specifically in diabetic tubuli. SIGNIFICANCE: In light of the increase in O-GlcNAc staining in the diabetic patients, we propose that increased O-GlcNAc levels might contribute to the development of diabetic nephropathy.

Crystal-storing histiocytosis associated with only one of two consecutive, but genetically unrelated B-cell lymphomas.

A localized crystal-storing histiocytosis (CSH) making the underlying marginal zone lymphoma (MZL) hardly discernible microscopically is described. Image analysis of the hyper electron dense crystals localized light microscopically in swollen histiocytic cells exhibited a major equatorial periodicity of 6.6 nm. Rarely, crystals of this type were detected within plasma cells, but were always surrounded by smooth membrane in contrast to Russell bodies. IgM/lambda restriction and VH3-21*02, DH4-17*01, JH4*02 gene usage were detected behind the lesion. Within 26 months, a genetically unrelated lymphoma of CD5-CD20-CD23-positive phenotype with a different VH1-24*01, DH2-21*02, JH2*01 heavy chain rearrangement, but with the same light chain gene usage, was identified without CSH. This might indicate that the unique condition responsible for the crystal formation is likely to rely on the sequence of the first clonally rearranged heavy chain exhibiting much higher CDRIII pI value (6.0) than the average.

Na+,K+-ATPase is modulated by angiotensin II in diabetic rat kidney--another reason for diabetic nephropathy?

Angiotensin II (ANGII) plays a central role in the enhanced sodium reabsorption in early type 1 diabetes in man and in streptozotocin-induced (STZ) diabetic rats. This study investigates the effect of untreated STZ-diabetes leading to diabetic nephropathy in combination with ANGII treatment, on the abundance and localization of the renal Na(+),K(+)-ATPase (NKA), a major contributor of renal sodium handling. After 7 weeks of STZ-diabetes (i.v. 65 mg kg(-1)) a subgroup of control (C) and diabetic (D7) Wistar rats were treated with ANGII (s.c. minipump 33 microg kg(-1) h(-1) for 24 h; CA and D7A). We measured renal function and mRNA expression, protein level, Serin23 phosphorylation, subcellular distribution, and enzyme activity of NKA alpha-1 subunit in the kidney cortex. Diabetes increased serum creatinine and urea nitrogen levels (C versus D7), as did ANGII (C versus CA, D7 versus D7A). Both diabetes (C versus D7) and ANGII increased NKA alpha-1 protein level and enzyme activity (C versus CA, D7 versus D7A). Furthermore, the combination led to an additive increase (D7 versus D7A, CA versus D7A). NKA alpha-1 Ser23 phosphorylation was higher both in D7 and ANGII-treated rats in the non-cytoskeletal fraction, while no signal was detected in the cytoskeletal fraction. Control kidneys showed NKA alpha-1 immunopositivity on the basolateral membrane of proximal tubular cells, while both D7 and ANGII broadened NKA immunopositivity towards the cytoplasm. Our study demonstrates that diabetes mellitus (DM) increases the mRNA expression, protein level, Ser23 phosphorylation and enzyme activity of renal NKA, which is further elevated by ANGII. Despite an increase in total NKA quantity in diabetic nephropathy, the redistribution to the cystosol suggests the Na(+) pump is no longer functional. ANGII also caused translocation from the basolateral membrane, thus in diabetic states where ANGII level is acutely elevated, the loss of NKA will be exacerbated. This provides another mechanism by which ANGII blockade is likely to be protective.

[Focal segmental glomerulosclerosis]. / Focalis segmentalis glomerulosclerosis.

Focal segmental glomerulosclerosis is a glomerular injury with typical morphology detectable by light microscopy. It has different histological subtypes and clinical symptoms. These different subtypes were recently systematized (Columbia classification). Focal segmental glomerulosclerosis is considered as the major type of podocytopathies, because podocytes are affected at each type of glomerular injury. Besides the primary forms of focal segmental glomerulosclerosis, an increased number of the secondary types are recognized. The wide use of drugs for renal protection in general and the long term administration of steroid therapy in some primary (idiopathic) cases are new elements among the therapeutic possibilities.

[Secondary IgA-nephropathy in gastroenterological diseases]. / Szekunder IgA-nephropathia gasztroenterológiai betegségekben.

IgA-nephropathy is the most common primary chronic glomerulonephritis worldwide. Beside the primary IgA-nephropathy (IgA-nephropathy with an unknown origin), there are more and more cases, which are associated with diseases of other organs. Although the causality is often not obvious, these forms are called secondary IgA-nephropathy. In this study, the authors cover only the secondary forms of IgA-nephropathy with relation to gastroenterology in a broader sense that includes the liver. They would like to draw the attention to the necessity of analyzing also the associate occurrence of gastrointestinal diseases (principally liver diseases, coeliac disease, Crohn's disease, ulcerative colitis) in patients with IgA-nephropathy, as well. They think that it would be expedient to organize a nationwide clinical analysis that would search the frequency of occurrence of IgA-nephropathy in the above mentioned gastrointestinal diseases.