Association of kidney fibrosis with urinary peptides: a path towards non-invasive liquid biopsies?

Chronic kidney disease (CKD) is a prevalent cause of morbidity and mortality worldwide. A hallmark of CKD progression is renal fibrosis characterized by excessive accumulation of extracellular matrix (ECM) proteins. In this study, we aimed to investigate the correlation of the urinary proteome classifier CKD273 and individual urinary peptides with the degree of fibrosis. In total, 42 kidney biopsies and urine samples were examined. The percentage of fibrosis per total tissue area was assessed in Masson trichrome stained kidney tissues. The urinary proteome was analysed by capillary electrophoresis coupled to mass spectrometry. CKD273 displayed a significant and positive correlation with the degree of fibrosis (Rho = 0.430, P = 0.0044), while the routinely used parameters (glomerular filtration rate, urine albumin-to-creatinine ratio and urine protein-to-creatinine ratio) did not (Rho = -0.222; -0.137; -0.070 and P = 0.16; 0.39; 0.66, respectively). We identified seven fibrosis-associated peptides displaying a significant and negative correlation with the degree of fibrosis. All peptides were collagen fragments, suggesting that these may be causally related to the observed accumulation of ECM in the kidneys. CKD273 and specific peptides are significantly associated with kidney fibrosis; such an association could not be detected by other biomarkers for CKD. These non-invasive fibrosis-related biomarkers can potentially be implemented in future trials

Incidence and outcomes of kidney replacement therapy for end-stage kidney disease due to primary glomerular disease in Europe:Findings from the ERA Registry

Background and hypothesis: Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death.Methods: We used data from the European Renal Association (ERA) Registry on 69,854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence, and survival.Results: The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidence of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium, and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had five-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death (adjusted hazard ratio: 1.8 [95% confidence interval: 1.6-1.9]) compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%).Conclusion: The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach

An unusual cause of rapidly progressive glomerulonephritis associated with ANCA vasculitis and ovarian malignancy – a relapse 39 years after initial treatment

A 69-year-old woman presented with severe anemia, proteinuria, microscopic hematuria and rapidly progressive renal failure. She was admitted to the nephrology department due to severe deterioration of renal function with complaints of malaise, fever, dry cough and occasional epistaxis that appeared 2 months prior to admission. Histopathologic examination of a specimen from kidney biopsy and immunologic findings revealed ANCA positive pauci-immune crescentic glomerulonephritis. The patient had a history of ovarian granulosa cell tumor and lung metastases that were treated surgically with postoperative radiotherapy and chemotherapy. Thoracic computed tomography showed tissue neoplasm in the right lung and ultrasound-guided percutaneous transthoracic biopsy confirmed granulosa cell tumor. That was a relapse, thirty-nine years after initial treatment of malignant disease and twenty-four years after surgical resection of metastases from both lungs. Although the association between malignancy and vasculitis has been well known for decades, this is the first described case of ANCA vasculitis associated with any type of gynecological malignancy and glomerulonephritis

Wide acquired arteriovenous fistula between main renal artery and interlobar vein treated with nephrectomy

A case of renal arteriovenous fistula between the main renal artery and interlobar vein diagnosed 25 years after percutaneous renal biopsy was presented. A 62-year-old female was referred to a urologist with dilatation of the left renal pyelocalyceal system diagnosed after abdominal ultrasonography, while intravenous urography did not confirm that finding. Historically, she underwent renal biopsy 25 years ago without any complication. Her hypertension was well controlled during the last 10 years, although three antihypertensive drugs with occasional additional diuretics were necessary during the last 6 months. Color Duplex Ultrasonography, arteriography and Multi-Slice Computed Tomography revealed the presence of renal arteriovenous fistula between the main renal artery and interlobar vein, as well as severe dilatation of all interlobar veins, renal, ovarian and adrenal vein on the left side. Urological and vascular surgeons operated to ligate the fistula and preserve the kidney. However, it was not possible to reach the fistula inside the kidney and nephrectomy was performed

The fractal and textural analysis of glomeruli in obese and non-obese patients

BackgroundFractal dimension is an indirect indicator of signal complexity. The aim was to evaluate the fractal and textural analysis parameters of glomeruli in obese and non-obese patients with glomerular diseases and association of these parameters with clinical features.MethodsThe study included 125 patients mean age 46 ± 15.2 years: obese (BMI ≥ 27 kg/m2—63 patients) and non-obese (BMI  0.05) compared to non-obese. Mean value of COR (t = 0.108) and IDM (t = 0.185) were almost the same in two patient groups. Obese patients had higher value of lacunarity (t = 0.499) in comparison with non-obese, the mean value of fractal dimension (t = 0.225) was almost the same in two groups. Significantly positive association between variance and creatinine concentration (r = 0.499, P < 0.01), significantly negative association between variance and CKD-EPI (r = -0.448, P < 0.01), variance and sex (r = -0.339, P < 0.05) were found.ConclusionsVariance showed significant correlation with serum creatinine concentration, CKD-EPI and sex. CON and IDM were significantly related to sex. Fractal and textural analysis parameters of glomeruli could become a supplement to histopathologic analysis of kidney tissue

Immunosuppressive regimens following kidney transplantation in five European countries: The observational RECORD study

Objective: To examine current immunosuppressive regimens administered to kidney transplant recipients (KTRs) in South-eastern Europe. Methods: This was a 12-month, multicenter, non- interventional, prospective, observational study of immunosuppressive regimens in adult de novo and maintenance KTRs. The primary endpoint was to identify the number, type, dosage and trough concentrations (C0) of immunosuppressive medications. Results: Data were available for 1774 KTRs from five countries (Bulgaria [n = 109], Croatia [n = 339], Romania [n = 647], Serbia [n = 434] and Slovenia [n = 245]). The most common immunosuppressive regimen in all countries was a triple therapy regimen (de novo KTRs, 67.9 – 100% at baseline and 67.3 – 100% at end of study ; maintenance KTRs, 48.8 – 90.7% and 43.2 – 90.1%, respectively). The most frequent regimen in de novo KTRs comprised tacrolimus, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), and corticosteroids. In maintenance KTRs, the most frequent regimen was tacrolimus or cyclosporine, and MMF or MPS, with or without corticosteroids. A C0 of <5 ng/mL was recorded in 40.2% of immediate-release and 48.7% of prolonged-release tacrolimus patients ; 79.5% of patients taking cyclosporine had a C0 of <75 ng/mL. Infections were the most common adverse event (358/597, 60.0%), mainly urinary tract infections (208/358, 58.1%). Conclusions: Triple therapy—comprising a calcineurin inhibitor (CNI ; tacrolimus or cyclosporine), antiproliferative drugs (MMF or MPS) and corticosteroids—was the most common immunosuppressive regimen used in KTRs in South- eastern Europe. Individual CNI C0 were below the target range in a substantial proportion of KTRs, highlighting the need to maintain therapeutic drug monitoring of immunosuppressive therapy in this patient population

Trends in kidney transplantation rate across Europe : study from the ERA Registry

Background The aim of this study was to identify trends in total, deceased donor (DD) and living donor (LD) kidney transplantation (KT) rates in European countries. Methods The European Renal Association (ERA) Registry and the Global Observatory on Donation and Transplantation (GODT) databases were used to obtain the number of KTs in individual European countries between 2010 and 2018. General population counts were obtained from Eurostat or the national bureaus of statistics. The KT rate per million population (p.m.p.) and the average annual percentage change (APC) were calculated. Results The total KT rate in the 40 participating countries increased with 1.9% annually [95% confidence interval (CI) 1.5, 2.2] from 29.6 p.m.p. in 2010 to 34.7 p.m.p. in 2018, reflecting an increase of 3.4 p.m.p. in the DD-KT rate (from 21.6 p.m.p. to 25.0 p.m.p.; APC 1.9%; 95% CI 1.3, 2.4) and of 1.5 p.m.p. in the LD-KT rate (from 8.1 p.m.p. to 9.6 p.m.p.; APC 1.6%; 95% CI 1.0, 2.3). The trends in KT rate varied widely across European countries. An East-West gradient was observed for DD-KT rate, with Western European countries performing more KTs. In addition, most countries performed fewer LD-KTs. In 2018, Spain had the highest DD-KT rate (64.6 p.m.p.) and Turkey the highest LD-KT rate (37.0 p.m.p.). Conclusions The total KT rate increased due to a rise in the KT rate from DDs and to a lesser extent from LDs, with large differences between individual European countries.Peer reviewe