Abstract Background Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have ...undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification. Case presentations Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6. Conclusions MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN.
Pediatric cystic kidney disease (CyKD) includes conditions characterized by renal cysts. Despite extensive research in this field, there are no reliable genetics or other biomarkers to estimate the ...phenotypic consequences. Therefore, CyKD in children heavily relies on clinical and diagnostic testing to predict the long-term outcomes.
A retrospective study aimed to provide a concise overview of this condition and analyze real-life data from a single-center pediatric CyKD cohort followed during a 12-year period.
Medical records were reviewed for extensive clinical, laboratory, and radiological data, treatment approaches, and long-term outcomes.
During the study period, 112 patients received a diagnosis of pediatric CyKD. Male patients were more involved than female (1:0.93). Fifty-six patients had a multicystic dysplastic kidney; twenty-one of them had an autosomal dominant disorder; fifteen had an isolated renal cyst; ten had been diagnosed with autosomal recessive polycystic kidney disease; three had the tuberous sclerosis complex; two patients each had Bardet-Biedl, Joubert syndrome, and nephronophthisis; and one had been diagnosed with the trisomy 13 condition. Genetic testing was performed in 17.9% of the patients, revealing disease-causing mutations in three-quarters (75.0%) of the tested patients. The most commonly presenting symptoms were abdominal distension (21.4%), abdominal pain (15.2%), and oligohydramnios (12.5%). Recurrent urinary tract infections (UTI) were documented in one-quarter of the patients, while 20.5% of them developed hypertension during the long-term follow-up. Antibiotic prophylaxis and antihypertensive treatment were the most employed therapeutic modalities. Seventeen patients progressed to chronic kidney disease (CKD), with thirteen of them eventually reaching end-stage renal disease (ESRD). The time from the initial detection of cysts on an ultrasound (US) to the onset of CKD across the entire cohort was 59.0 (7.0-31124.0) months, whereas the duration from the detection of cysts on an US to the onset of ESRD across the whole cohort was 127.0 (33.0-141.0) months. The median follow-up duration in the cohort was 3.0 (1.0-7.0) years. The patients who progressed to ESRD had clinical symptoms at the time of initial clinical presentation.
This study is the first large cohort of patients reported from Croatia. The most common CyKD was the multicystic dysplastic kidney disease. The most common clinical presentation was abdominal distention, abdominal pain, and oliguria. The most common long-term complications were recurrent UTIs, hypertension, CKD, and ESRD.
Nephrotic syndrome may persist despite end-stage kidney disease and result in dyslipidaemia, thrombosis and a significantly increased cardiovascular risk. Treatment of refractory nephrotic syndrome ...includes surgical bilateral nephrectomy, renal artery embolization and pharmacologic nephrectomy.
We present a case of a haemodialysis patient with refractory nephrotic syndrome who underwent pharmacologic nephrectomy. The procedure decreased the patient's cardiovascular risk and enabled the patient to become a candidate for kidney transplantation.
In certain situations residual renal function may be harmful. In such instances, nephrectomy should be considered. Pharmacologic nephrectomy using nephrotoxic drugs is a non-invasive approach with least potential complications.
Autosomal dominant polycystic kidney disease (ADPKD) is one of the leading causes of end-stage renal disease. In spite of the recent tremendous progress in the understanding of ADPKD pathogenesis, ...the molecular mechanisms of the disease remain incompletely understood. Considering emerging new targeted therapies for ADPKD, it has become crucial to disclose easily measurable and widely available biomarkers for identifying patients with future rapid disease progression. This review encompasses all the research with a shared goal of identifying promising serum or urine biomarkers for predicting ADPKD progression or response to therapy. The rate of the ADPKD progress varies significantly between patients. The phenotypic variability is only partly explained by the underlying genetic lesion diversity. Considering significant decline in kidney function in ADPKD is not usually evident until at least 50% of the parenchyma has been destroyed, conventional kidney function measures, such as glomerular filtration rate (GFR), are not suitable for monitoring disease progression in ADPKD, particularly in its early stages. Since polycystic kidney enlargement usually precedes the decline in GFR, height-adjusted total kidney volume (ht-TKV) has been accepted as an early biomarker for assessing disease severity in ADPKD patients. However, since measuring ht-TKV is time-consuming and observer-dependent, the identification of a sensitive and quickly measurable biomarker is of a great interest for everyday clinical practice. Throughout the last decade, due to development of proteomic and metabolomic techniques and the enlightenment of multiple molecular pathways involved in the ADPKD pathogenesis, a number of urine and serum protein biomarkers have been investigated in ADPKD patients, some of which seem worth of further exploring. These include copeptin, angiotensinogen, monocyte chemoattractant protein 1, kidney injury molecule-1 and urine-to-plasma urea ratio among many others. The aim of the current review is to provide an overview of all of the published evidence on potentially clinically valuable serum and urine biomarkers that could be used for predicting disease progression or response to therapy in patients with ADPKD. Hopefully, this review will encourage future longitudinal prospective clinical studies evaluating proposed biomarkers as prognostic tools to improve management and outcome of ADPKD patients in everyday clinical practice.
Concomitant treatment with drugs that inhibit drug metabolising enzymes and/or transporters, such as commonly prescribed statins and nonsteroidal anti-inflammatory drugs (NSAIDs), has been associated ...with prolonged drug exposure and increased risk of adverse drug reactions (ADRs) due to drug-drug interactions. The risk is further increased in patients with chronic diseases/comorbidities who are more susceptible because of their genetic setup or external factors. In that light, we present a case of a 46-year-old woman who had been experiencing acute renal and hepatic injury and myalgia over two years of concomitant treatment with diclofenac, atorvastatin, simvastatin/fenofibrate, and several other drugs, including pantoprazole and furosemide. Our pharmacogenomic findings supported the suspicion that ADRs, most notably the multi-organ toxicity experienced by our patient, may be owed to drug-drug-gene interactions and increased bioavailability of the prescribed drugs due to slower detoxification capacity and decreased hepatic and renal elimination. We also discuss the importance of CYP polymorphisms in the biotransformation of endogenous substrates such as arachidonic acid and their modulating role in pathophysiological processes. Yet even though the risks of ADRs related to the above mentioned drugs are substantially evidenced in literature, pre-emptive pharmacogenetic analysis has not yet found its way into common clinical practice.
The most common cause of rapidly progressive glomerulonephritis in elderly, antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN), demands immunosuppressive therapy (IS) regimen ...in a multi-morbid disease burdened population. Our aim was to assess outcome differences in two age groups. The study included a total of 38 ANCA-GN renal limited patients (18 men) treated from 1990 to 2018, of which 11 were 65 years of age and older (median 70, min. - max. 66 - 79 years), and 27 younger than 65 (median 55, min. - max. 23 - 64 years). All patients were treated with mono/combination of IS. Most commonly applied IS in elderly was combination of IV cyclophosphamide and corticosteroids (CS) (in 9 81.8%), while in younger it was a combination of CS and cyclophosphamide or rituximab (59.2%). Older patients had comparable mortality (3, 14.8% vs. 4, 27.3%; P = 0.369), malignancies (1, 3.7% vs. 1, 9.1%; P = 0.5) and infectious complications (10, 46.7% vs. 7, 63.6%; P = 0.388). Ten patients at the end of the follow up were at renal replacement therapy (RRT), with no difference between age groups (6, 22.2% vs. 4, 36.4%; P = 0.369). Interestingly, from initial need for RRT, half of the younger and older patients recovered with IS. Our findings give more credit to the current paradigm to treat elderly ANCA-GN patients with IS therapy due to the similar outcome of elderly as younger ones. Key words: Antineutrophil Cytoplasmic antibodies, Glomerulonephritis, elderly, Immunosuppression, Mortality, Kidney failure
Current knowledge on histopathological changes occurring after COVID‐19 in transplanted kidneys is limited. Herein, we present renal allograft pathology findings in patients recovered from COVID‐19.
...Six patients underwent indication biopsy, and one required allograft nephrectomy after acute COVID‐19. Demographic data, clinical characteristics, and laboratory findings were recorded. The histopathological analysis included light microscopy, immunostaining, and electron microscopy.
Five patients were hospitalized for acute COVID‐19, and all were diagnosed with imaging‐confirmed pneumonia, one requiring mechanical ventilation, and two requiring dialysis. Two patients had mild form. Histopathologic examination of renal allograft specimens revealed collapsing, perihilar, tip‐lesion and secondary FSGS in one patient each. One patient had borderline acute cellular rejection, and two had chronic antibody‐mediated rejection. Histopathologic changes of glomerular tufts were accompanied by acute tubular injury in four patients. None of our patients had signs of viral inclusions in kidney cells.
One patient died and one remained dialysis‐dependent after the good initial response to treatment. Patients with collapsing and perihilar FSGS had further progression of their chronic allograft nephropathy still without need for dialysis.
In conclusion, diverse kidney pathology may be found in SARS‐CoV‐2–infected renal transplant patients. It seems that viral infection may affect the immune system with triggering of glomerular diseases, while the acute tubular injury is of multifactorial etiology. Direct viral effect is less likely.
Introduction: primary membranous nephropathy (pMN) is glomerulopathy caused in the majority of cases by autoantibodies to Phospholipase-A2 receptors (PLA2R-AB). This study aimed to evaluate the ...clinical course and outcomes of the patients with pMN regarding PLA2R-AB status. Patients and methods: 32 patients (21 males, 11 females) with renal biopsy-proven pMN were included in the study. PLA2R-AB (ELISA method) and outcomes (defined according to KDIGO) were evaluated after 21 and 64 months of follow-up in 28 patients. Results: 19 patients had positive PLA2R-AB (>20 RU/ml) (59.3%), with median titer of 97 (21-1418 RU/ml). The rate of remission in low PLA2R-AB titer group (< 200 RU/ml) after 21 months was significantly higher than in high PLA2R-AB group (> 200 RU/ml) (90% vs. 50%, p=0.045), and after 64 months the difference was not significant (80% vs. 50%, p=0.210).The relapse rate after 64 months was higher in the high PLA2R-AB group (87% vs. 63%). Multivariant linear regression found serum creatinine (beta=0.682, p<0.001) and PLA2R-AB (beta=0.527, p<0.001) as significant predictors for kidney function at the end of follow-up. Conclusion: higher titers of PLA2R-AB are related to worse kidney function outcome, higher 24-hour proteinuria, and a higher number of relapses in patients with pMN. Key words: membranous nephropathy, M-type phospholipase A2 receptor, autoantibodies, glomerulonephritis
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