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Competing Interests: All authors declare no conflict of interest.

Alport syndrome (AS) is a severe inherited glomerulopathy caused by mutations in the genes encoding the α-chains of type-IV collagen, the most abundant component of the extracellular glomerular basement membrane (GBM). Currently most AS mouse models are knockout models for one of the collagen-IV genes. In contrast, about half of AS patients have missense mutations, with single aminoacid substitutions of glycine being the most common. The only mouse model for AS with a homozygous knockin missense mutation, Col4a3-p.Gly1332Glu, was partly described before by our group. Here, a detailed in-depth description of the same mouse is presented, along with another compound heterozygous mouse that carries the glycine substitution in trans with a knockout allele. Both mice recapitulate essential features of AS, including shorten lifespan by 30-35%, increased proteinuria, increased serum urea and creatinine, pathognomonic alternate GBM thinning and thickening, and podocyte foot process effacement. Notably, glomeruli and tubuli respond differently to mutant collagen-IV protomers, with reduced expression in tubules but apparently normal in glomeruli. However, equally important is the fact that in the glomeruli the mutant α3-chain as well as the normal α4/α5 chains seem to undergo a cleavage at, or near the point of the mutation, possibly by the metalloproteinase MMP-9, producing a 35 kDa C-terminal fragment. These mouse models represent a good tool for better understanding the spectrum of molecular mechanisms governing collagen-IV nephropathies and could be used for pre-clinical studies aimed at better treatments for AS., (© 2021 The Authors.)

In this article six patients with hypokalemic metabolic alkalosis, classified as Bartter or Gitelman syndrome are presented. Both syndromes result from different gene mutation inducing impaired function of the transporters involved in sodium, chloride and potassium reapsorption in thick ascending limb of the loop of Henle and distal convoluted tubules. These syndromes typically present with hypokalemia, metabolic alkalosis, hyperreninemic hyperaldosteronism without hypertension, polyuria and muscle weakness. Other clinical characteristics may vary considerably, depending on the gene expression. Correct diagnosis is only possible using expensive and not-routinely available genetic testing. Routine laboratory tests, especially those considering serum and urine electrolytes, can help in recognizing these syndromes and therefore in timely beginning of treatment. The most important distinctive laboratory findings are serum magnesium concentration and urine calcium excretion. In Bartter syndrome typically there is hypercalciuria with or without hypomagnesemia, while in Gitelman syndrome typical findings are hypocalciuria and hypomagnesemia. Recognizing and treating these patients is important due to possible increased morbidity and mortality induced by severe electrolyte imbalance.

C1q nephropathy is considered a form of glomerulonephritis, defined by histological findings of dominant Clq immune deposits in renal biopsy. It is a rare disease, most often manifested in children and young adults. The most common clinical manifestation of the disease is nephrotic syndrome, but other renal syndromes could also be found. The cause of the disease is not known, but the immune pathogenesis could be assumed. Often, resistance to glucocorticoid or other immunosuppressive therapy is present, potentially leading to chronic renal insufficiency. We present ten patients with renal biopsy and clinical findings of Clq nephropathy. None of the patients had clinical or serological manifestations of systemic lupus. All patients had normal findings of C3 and C4 components of complement, as well as normal ANF, anti-dsD-NA and ANCA antibodies.

Objectives: Chronic transplant dysfunction after kidney transplantation is a major reason of kidney graft loss and is caused by immunological and non-immunological factors. There is evidence that mycophenolate mofetil (MMF) may exert a positive effect on renal damage in addition to immunosuppression, by its direct antifibrotic properties. The aim of our study was to retrospectively investigate the role of MMF doses on progression of chronic allograft dysfunction and fibrosis and tubular atrophy (IF/TA)., Setting: Retrospective, cohort study., Participants: Patients with kidney transplant in a tertiary care institution. This is a retrospective cohort study that included 79 patients with kidney and kidney-pancreas transplantation. Immunosuppression consisted of anti-interleukin 2 antibody induction, MMF, a calcineurin inhibitor±steroids., Primary Outcome Measures: An association of average MMF doses over 1 year post-transplant with progression of interstitial fibrosis (Δci), tubular atrophy (Δct) and estimated-creatinine clearance (eCrcl) at 1 year post-transplant was evaluated using univariate and multivariate analyses., Results: A higher average MMF dose was significantly independently associated with better eCrcl at 1 year post-transplant (b=0.21±0.1, p=0.04). In multiple regression analysis lower Δci (b=-0.2±0.09, p=0.05) and Δct (b=-0.29±0.1, p=0.02) were independently associated with a greater average MMF dose. There was no correlation between average MMF doses and incidence of acute rejection (p=0.68)., Conclusions: A higher average MMF dose over 1 year is associated with better renal function and slower progression of IF/TA, at least partly independent of its immunosuppressive effects., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Unilateral ureteral obstruction (UUO) results in a number of pathophysiological and morphological changes in the renal parenchyma, including interstitial inflammation and fibrosis, apoptotic changes of tubular and interstitial cells. Recent studies have indicated an association between renin-angiotensin system and apoptotic alterations in the kidney after unilateral obstructive nephropathy. In this study, the effect of ACE inhibitors and AT1 receptor antagonists on tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy after UUO in rats was investigated. The study was conducted on Wistar rats with unilaterally ligated ureter and sham operated animals (control group). The rats with UUO were treated with ACE inhibitor (cilazapril) or AT1 receptor antagonists (losartan) and control group was treated with H2O. Sham-operated animals were treated in the same way. Tubular and interstitial cell apoptosis was detected morphologically by hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL). The area of intersitial fibrosis was determined using computer-assisted image processing after Gomory silver impregnation of paraffin sections. All experimental animal groups with unilateral ureter ligation showed a significantly increased number of apoptotic tubular and interstitial cells in the obstructed kidney compared with the contralateral, unobstructed kidney. Histomorphometric analysis of renal interstitial fibrotic changes in the groups of rats treated with losartan or water showed a statistically significant difference (p < 0.05) between the operated and sham--operated animals. In conclusion, following UUO there is a significantly increased number of apoptotic tubular cells and interstitial fibrosis in the ipsilateral kidney compared with the contralateral kidney. ACE inhibitors and AT1 receptor antagonists could not decrease the extent of renal cells apoptosis and interstitial fibrosis after UUO.

Background: Nephrotic syndrome (NS) is pathological condition characterized by heavy proteinuria. Our study investigates hypothesis that change in cell proliferation of proximal tubules influences primary cilia structure and function and promotes cystogenesis in congenital nephrotic syndrome of the Finnish type (CNF) and focal segmental glomerulosclerosis (FSGS)., Methods: CNF kidneys were analyzed genetically. Proliferation (Ki-67), apoptosis (caspase-3), and primary cilia (α-tubulin) length and structure were analyzed immunohistochemically and ultrastructurally in healthy, CNF and FSGS kidneys. Cyst diameters were measured and correlated with proliferation index., Results: Proximal tubules cells of healthy kidneys did not proliferate. In nephrotic kidneys, tubules with apparently normal diameter covered by cuboidal/columnar epithelium (PTNC) contained 81.54% of proliferating cells in CNF and 36.18% in FSGS, while cysts covered with columnar epithelium (CC) contained 37.52% of proliferating cells in CNF and 45.23% in FSGS. The largest cysts, covered with squamous epithelium (CS) had 11.54% of proliferating cells in CNF and 13.76% in FSGS. Increase in cysts diameter correlated with changes in proliferation index, tubular cells shape, primary cilia formation and appearance of apoptotic cells., Conclusions: We present a novel histopathological data on the structure and possible changes in function of tubular cell in NS kidneys during cystogenesis. We suggest existence of common principles of cystogenesis in CNF and FSGS kidneys, including serious disturbances of tubular cells proliferation and apoptosis, and faulty primary cilia signaling leading to deterioration of proteinuria in NS kidneys.

In December 2005, the 55-year-old patient was hospitalized because of acute kidney failure and suspected hemorrhagic fever. The physical examination showed splenomegaly (spleen ultrasound-18 cm in large diameter, and 11 cm by palpation) with thrombocytopenia and anemia. He underwent kidney biopsy which described infiltration of small B cell lymphocytes with positive lambda chains. His bone marrow showed infiltration of atypical lymphocytes, and flow cytometry was typical of B-cell CLL. Patient started therapy with corticosteroids (methylprednisolone 80 mg iv) and continued treatment with prednisone (Decortin 20 mg tablets) and chlorambucil (Leukeran 16 mg tablets) through three days. An addition to therapy lead to an increase in platelet count, creatinine level decline and recovery of renal function was observed. He was treated with 6 cycles of therapy with prednisone and chlorambucil and achieved a satisfactory therapeutic effect with adequate hematologic parameters and less severe splenomegaly. Maintenance therapy was continued with prednison at daily dose of 10 mg. Our patient is one of the amongst previously reported as an example of a rare complication of CLL'with leukemic infiltrate causing acute renal insufficiency. Renal biopsy is necessary to confirm the diagnosis. This complication appears to respond well to a variety of treatments. Our patient achieved complete resolution of renal failure and partial hematological response with combination of chlorambucil and prednisone.

Fibrillary glomerulonephritis and immunotactoid glomerulopathy belong to the rare renal disorders characterized by formation of the organized glomerular deposits. Pathogenesis of these disorders is still not fully clarified but they could appear as a primary condition or be regarded as a part of the various systemic mainly lymphoproliferative disorders. Clinical presentation includes proteinuria, hematuria, arterial hypertension and progressive renal insufficiency during several years. In this work we presented a male patient with fibrillary glomerulonephritis and a female patient with immunotactoid glomerulopathy as a part of a non-Hodgkin lymphoma. The aim of this presentation is to show the features of the fibrillary glomerulonephritis and immunotactoid glomerulopathy as well as emphasize the significance of the electron microscopy in the identification of these uncommon entities.

The allergic interstitial nephritis (AIN) is a rare renal disorder which is commonly clinically presented with an acute renal failure. AIN is the most frequent result of the hypersensitivity related to drugs (most often antibiotics). In the patients with clinical suspicion to a drug related AIN, kidney biopsy is the most important diagnostic procedure. Except of causative drug discontinuation, AIN therapy is based on high dose glucocorticoids 1 mg/kg/day with dose tapering during consecutive 3 months. In the present work, we have shown 10 patients with drug induced AIN. We identified 4 causative drug groups among which most frequent were antibiotics. In clinical presentation of our patients acute renal failure was dominant and median of baseline serum creatinine was 497.5 micromol/L. In all patients the kidney biopsy was performed and nine patients (90%) have been treated with recommended glucocorticoid regimen, additionally, in 3 patients hemodialysis was introduced. In all patients, reduction in serum creatinine value was achieved with serum creatinine median of 152 micromol/L after a three-month glucocorticoid treatment (p=0.018).