Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are part of the spectrum of kidney disorders caused by pathogenic variants in α3, α4, or α5 chains of the collagen type IV, the ...major structural component of the glomerular basement membrane (GBM). Using targeted next-generation sequencing (NGS), 34 AS/TBMN patients (58.8% male) from 12 unrelated families were found positive for heterozygous c.2881+1G>A variant of the COL4A3gene, that is considered disease-causing. All patients were from the continental or island part of Croatia. Clinical, laboratory, and histopathological data collected from the medical records were analyzed and compared to understand the clinical course and prognosis of the affected patients. At the time of biopsy or first clinical evaluation, the mean age was 31 years (median: 35 years; range: 1 - 72 years). Hematuria was present in 33 patients (97.1%) and 19 (55.9%) patients had proteinuria. There were 6 (17.6%) patients with hearing loss, 4 (11.8%) with ocular lesions, and 11 (32.4%) with hypertension. Twenty-three (67.6%) patients had proteinuria at follow-up, and 5 (14.7%) patients with the median age of 48 years (range: 27-55) progressed to kidney failure, started dialysis, or underwent kidney transplantation. Of the 13 patients who underwent kidney biopsy, 4 (30.8%) developed focal segmental glomerulosclerosis (FSGS), and 8 (66.7%) showed lamellation of the GBM, including all patients with FSGS. It is essential to conduct a detailed analysis of each collagen type IV genetic variant to optimize the prognosis and therapeutic approach for affected patients.
Anti-glomerular basement membrane (anti-GBM) disease is an acute and life-threatening systemic autoimmune disorder. The coexistence of circulating anti-neutrophil cytoplasmic antibodies (ANCA) and ...anti-GBM disease, the so-called double-positive disease (DPD), is exceptionally rare. We report a unique case of DPD manifesting as pulmonary-renal syndrome (PRS) in a 46-year-old woman who first presented with clinical and radiological suspicion of pneumonia. Chest computed tomography scan later revealed bilateral alveolar hemorrhage. Kidney biopsy showed necrotizing crescentic (100% glomeruli) glomerulonephritis. On immunofluorescence microscopy, glomeruli were global linear positive for IgG, confirming anti-GBM disease. Double positivity was detected for circulating anti-myeloperoxidase ANCA (p-ANCA) and anti-GBM antibodies. Acute renal failure evolved rapidly. Therapeutic plasma exchange (TPE) and hemodialysis (HD) were initiated early in combination with intravenous pulse corticosteroid therapy followed by oral methylprednisolone and cyclophosphamide. Pulmonary hemorrhage resolved, but renal function could not be preserved. The patient remains HD dependent. This case report highlights that pulmonary symptomatology may be the leading clinical presentation of PRS, with initially normal renal function at DPD onset. Early recognition and diagnosis are therefore crucial to timely clinical intervention. The role of prompt kidney biopsy and initiation of TPE and HD in PRS must not be underestimated.
Glomerulonephritis following an enterococcal endocarditis is an extremely rare and life-threatening condition. We present the case of a 71-year-old patient with rapidly progressive glomerulonephritis ...following enterococcal endocarditis after surgical replacement of the aortic valve. The combination of antibiotic therapy, corticosteroid therapy and haemodialysis led to an improvement in renal function; however, the severity of cardiac deterioration resulted in a fatal outcome.
Cystinuria is an autosomal recessive disease that leads to recurrent stone formation. Tiopronin, a glycine derivative with a free thiol similar to penicillamine, prevents stone formation and ...facilitates their dissolution. Nephrotic-range proteinuria is a serious and relatively uncommon adverse effect, reported in 6-10% of patients, most frequently during the first year of tiopronin use. Various patterns of morphologic kidney injury have been associated with tiopronin use, including MCD, MN, and MPGN. Acute interstitial nephritis can be caused virtually by any drug. Non-steroidal anti-inflammatory drugs (NSAIDs) may cause AIN, with or without nephrotic syndrome due to minimal change disease or membranous nephropathy. Key words: tiopronin, NSAID, acute interstitial nephritis
Since the beginning of mass vaccination against coronavirus disease 2019 (COVID-19), vaccine-linked immune-mediated diseases have been increasingly reported. The development of these diseases after ...COVID-19 vaccination may be attributed to the mechanisms of molecular mimicry and cross-reactivity between the viral spike protein and self-antigens. The most frequent vaccine-linked glomerular disease is immunoglobulin A nephropathy (IgAN). Cutaneous vasculitis has also been reported after COVID-19 vaccination. In both diseases, deposition of immune complexes activates the inflammatory response with end-organ damage. We report on a case of de novo IgAN in a young man and a case of severe cutaneous vasculitis in a 68-year-old woman, both after the second dose of Pfizer-BioNTech COVID-19 vaccine. Neither of the patients had a history of autoimmunity or adverse reactions to vaccines. The temporal association between vaccination and disease development in the absence of other possible intercurrent inciting events suggests a causal mechanism, although coincidental co-occurrence cannot be excluded. In both cases, immunosuppressive treatment was warranted to stop disease progression and to partially or completely resolve the disease. A timely reaction is needed if new-onset signs of an immune-mediated disease appear after vaccination.
To present the pathohistological and clinical characteristics of five Croatian families with Alport spectrum disorders caused by splice acceptor pathogenic variant c.193-2A>C in COL4A4 at the genomic ...position chr2:227985866.
The study enrolled five probands with kidney biopsy analysis and five family members. Mutation screening was performed with Illumina MiSeq platform. The pathogenic variant was confirmed with standard dye-terminator sequencing.
The only homozygous patient, aged two, had proteinuria and hematuria with preserved kidney function and no extrarenal manifestations. This patient had changes characteristic for Alport syndrome observed on electron microscopy of the kidney biopsy. In the heterozygous group, six patients had hematuria, four biopsied probands had proteinuria, and only one had moderately reduced kidney function. Heterozygous probands had variable kidney biopsy findings. Three patients had thin glomerular basement membrane nephropathy visible on electron microscopy and focal segmental glomerulosclerosis on light microscopy, two of them with focal lamellation on electron microscopy. One heterozygous patient had changes characteristic for Alport syndrome on electron microscopy without focal segmental glomerulosclerosis.
The homozygous patient had hematuria and proteinuria with preserved kidney function. The heterozygous patients presented with reasonably mild clinical phenotype and variable pathohistological findings.
Uvod: IgA-nefropatija (IgAN) ima varijabilnu prezentaciju i prognozu. Međunarodni alat za predviđanje rizika u IgAN-u (IgAN-PT, od engl. International IgA Nephropathy Prediction Tool) predviđa ...napredovanje bubrežne bolesti do završnog stupnja ili smanjenje procijenjene glomerulske filtracije (eGFR) za 50%. Preporučuje se optimalna suportivna terapija najmanje tri mjeseca, praćena šestomjesečnom primjenom glukokortikoida samo u bolesnika s velikim rizikom napredovanja. Cilj: Istražiti koji su bolesnici imali veću vjerojatnost primiti imunosupresivnu terapiju (IS) te ishode liječenih IS-om. Ispitanici i metode: Retrospektivno kohortno istraživanje 48 bolesnika (33 muškarca), medijana dobi 50 godina (interkvartilni raspon, IQR, od engl. interquartile range 35 – 59), medijana praćenja 43 mjeseca (IQR 18 – 54), liječenih u Kliničkoj bolnici Merkur s novodijagnosticiranim idiopatskim IgAN-om u razdoblju od 2012. do 2021. godine. Rezultati: Imunosupresiju je primilo 17 bolesnika i oni su češće imali mezangijsku (M) (82% prema 54%, p=0,05), endokapilarnu hipercelularnost (E) (65% prema
21%, p=0,004) i polumjesece (C) (41% prema 14%, p=0,04). U odnosu na one bez IS-a nije bilo značajne razlike u eGFR-u kod biopsije (52 (IQR 38 – 81) prema 46 (IQR 30 – 72) ml/min/1,73 m2, p<0,05), ali su liječeni IS-om imali veću eGFR nakon dvije godine praćenja (66 IQR 37 – 97 prema 34 IQR 20 – 56 ml/min/1,73 m2, p=0,02). Omjer proteina prema kreatininu u urinu (uPCR) smanjio se nakon liječenja (kod biopsije, 106 IQR 50 – 317 prema završnom 47 IQR 20 – 129 mg/mmol), a nije bilo razlike u početnom i završnom uPCR između
onih koji jesu i nisu primali IS. Zbroj IIgAN se smanjio nakon liječenja (10,56% ± 12,66% prema 8,45% ± 9,22%, p=0,01), bez razlike u smanjenju između liječenih i neliječenih IS-om. Zaključci: Bolesnici s većim M, E i C su bili češće liječeni IS-om i oni su imali bolju eGFR nakon dvije godine; uPCR i zbroj IIgAN na kraju praćenja bili su manji neovisno o IS-u.
Collapsing glomerulopathy (CG) or collapsing focal segmental glomerulosclerosis (cFSGS) is an aggressive disease with a high tendency of progression to end-stage renal disease due to common ...resistance to conventional immunosuppressants. Rituximab (RTX), a monoclonal antibody against CD20 B cells, showed some benefit in the treatment of CG. We are reporting about female patients with an idiopathic form of CG presenting with nephrotic syndrome (NS) and renal insufficiency resistant to several immunosuppressive agents such as steroids (ST), calcineurin inhibitors (CNI), and cyclophosphamide (CYC). This multidrug-resistant disease responded to RTX with complete remission. Forty-four months after initial RTX administration, a relapse of CG with severe NS and acute renal insufficiency occurred. Repeated application of RTX led to complete remission again. To the best of our knowledge, we are reporting the first case of the relapsing multidrug-resistant form of CG, which responded to RTX. Current data about the treatment of CG with RTX is lacking and is based on rare case reports and small case series. Thus, our report can contribute to determining the role of RTX in the treatment of CG.
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