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Fabry disease (FD) is a rare, X-linked, lysosomal storage multisystemic disorder which may lead to kidney failure and require kidney transplantation (KT). Data on long-term kidney allograft outcomes and the evolution of systemic FD under dis-ease-specific therapy after KT remain limited. We retrospectively evaluated six kidney transplant recipients (KTRs) with FD followed in our center for median tine after KT of 7 years (range, 4-13). Five patients (83.3%) were males and five had a classic Fabry phe-notype. At last follow-up patient survival was 100% and five out of six KTR had a func-tional kidney graft. Among KTRs with a functioning graft, the median change is esti-mated glomerular filtration rate from 1-year to last follow-up was +3.3 ml/min/1.73m2 (range, -50.7 to +10.5), while proteinuria remained low. One patient developed late an-tibody-mediated rejection with de novo donor-specific antibodies and graft loss at 8 years post-transplantation. Five KTRs were receiving enzyme replacement therapy at the time of KT. Three patients were subsequently switched to migalastat and two later returned to enzyme replacement therapy. Lyso-Gb3 and cardiac structural parameters showed heterogenous longitudinal trajectories despite generally preserved kidney graft function. No cardiovascular events occurred during follow-up. These findings support KT as an effective renal replacement therapy in FD and highlight the need for contin-uous Fabry-specific therapy and multidisciplinary surveillance after transplantation.

Background: Molecular analysis in patients with nephrolithiasis (NL) and/or nephrocalcinosis (NC) enables more accurate evaluation of underlying etiologies. The existing clinical evidence regarding genetic testing in adults with NL comprises only a few cohort studies. Materials and Methods: We retrospectively analyzed 49 adult patients diagnosed with NL and/or NC from a single center, on whom we performed a genetic test using a nephrolithiasis panel. We reviewed the phenotype of the patients and compared the cases with positive and negative molecular diagnosis. Results: In total, 49 adult patients with NL and/or NC underwent genetic testing. Of the tested patients, 29 (59.2%) patients had 24 abnormal variants in 14 genes. Mendelian diseases were diagnosed in 14 (28.6%) cases: cystinuria (SLC3A1, SLC7A9; n = 4), hereditary distal renal tubular acidosis (SLC4A1; n = 3), Dent disease (CLCN5; n = 2), familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (CLDN16; n = 1), infantile hypercalcemia type 1 (CYP24A1; n = 1), primary hyperoxaluria type 1 (AGXT; n = 1), Bartter syndrome type 2 (KCNJ1; n = 1), and autosomal dominant tubulointerstitial kidney disease (UMOD; n = 1). Eight (16.3%) patients had pathogenic or likely pathogenic monoallelic variants as predisposing factors for NL and/or NC, and seven (14.3%) had biallelic or monoallelic variants of uncertain significance. Patients with positive genetic tests had a lower estimated glomerular filtration rate (p = 0.03) and more frequent NL associated with NC (p = 0.007) and were unlikely to have arterial hypertension (p = 0.03) when compared with patients with negative tests. Conclusions: Our study shows an increased effectiveness of molecular diagnosis and highlights the benefits of genetic testing. NL associated with NC and the presence of chronic kidney disease are the characteristics that should prompt the clinician to suspect an inherited form of NL and/or NC.

Background: Molecular analysis in patients with nephrolithiasis (NL) and/or nephrocalcinosis (NC) enables an accurate evaluation. The existing clinical evidence regarding genetic testing in adults with NL is comprised of only a few cohort studies. Materials and methods: We retrospectively analyzed 49 adult patients diagnosed with NL and/or NC from a single center, on whom we performed a genetic test using a nephrolithiasis panel. We reviewed the phenotype of the patients and compared the cases with positive and negative molecular diagnosis. Results: 49 adult patients with NL and/or NC underwent genetic testing. Of the tested patients, 29 (59.2%) patients had 24 abnormal variants in 14 genes. Mendelian diseases were diagnosed in 14 (28.6%) cases: cystinuria (SLC3A1, SLC7A9; n=4), hereditary distal renal tubular acidosis (SLC4A1; n=3), Dent disease (CLCN5; n=2), familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (CLDN16; n=1), infantile hypercalcemia type 1 (CYP24A1; n=1), primary hyperoxaluria type 1 (AGXT; n=1), Bartter syndrome type 2 (KCNJ1; n=1) and autosomal dominant tubulointerstitial kidney disease (UMOD; n=1); 8 (16.3%) patients had pathogenic or likely pathogenic monoallelic variants as predisposing factors for NL and/or NC, and 7 (14.3%) had biallelic or monoallelic variants of uncertain significance (VUS). Patients with positive genetic tests had a lower estimated glomerular filtration rate (p=0.03), had more frequently NL associated with NC (p=0.007), and were unlikely to have arterial hypertension (p=0.03) when compared with patients with negative test. Conclusions: Our study shows an increased effectiveness of molecular diagnosis and highlights the benefits of genetic testing. NL associated with NC and the presence of chronic kidney disease are the characteristics that should prompt the clinician to suspect an inherited form of NL and/or NC.

Background: Data on diuretic treatment in nephrotic syndrome (NS) are scarce. Our goal was to assess the non-inferiority of the combined oral diuretics (furosemide/hydrochlorothiazide/amiloride) compared to intravenous (i.v.) furosemide in patients with NS and resistant edema. Methods: We conducted a prospective randomized trial on 22 patients with resistant nephrotic edema (RNE), defined as hypervolemia and a FENa < 0.2%. Based on a computer-generated 1:1 randomization, we assigned patients to receive either intravenous furosemide (40 mg bolus and then continuous administration of 5 mg/h) or oral furosemide (40 mg/day) and hydrochlorothiazide/amiloride (50/5 mg/day) for a period of 5 days. Clinical and laboratory measurements were performed daily. Hydration status was assessed by bioimpedance on day 1 and at the end of day 5 after treatment initiation. The primary endpoint was weight change from baseline to day 5. Secondary endpoints were hydration status change measured by bioimpedance and safety outcomes (low blood pressure, severe electrolyte disturbances, acute kidney injury and worsening hypervolemia). Results: Primary endpoint analysis showed that after 5 days of treatment, there was a significant difference in weight change from baseline between groups [adjusted mean difference: −3.33 kg (95% CI: −6.34 to −0.31), p = 0.03], with a higher mean weight change in the oral diuretic treatment group [−7.10 kg (95% CI: −18.30 to −4.30) vs. −4.55 kg (95%CI: −6.73 to −2.36)]. Secondary endpoint analysis showed that there was no significant difference between groups regarding hydration status change [adjusted mean difference: −0.05 L (95% CI: −2.6 to 2.6), p = 0.96], with a mean hydration status change in the oral diuretic treatment group of −4.71 L (95% CI: −6.87 to −2.54) and −3.91 L (95% CI: −5.69 to −2.13) in the i.v. diuretic treatment group. We observed a significant decrease in adjusted mean serum sodium of −2.15 mmol/L [(95% CI: −4.25 to −0.05), p = 0.04]), favored by the combined oral diuretic treatment [−2.70 mmol/L (95% CI: −4.89 to −0.50) vs. −0.10 mmol/L (95%CI: −1.30 to 1.10)]. No statistically significant difference was observed between the two groups in terms of adverse events. Conclusions: A combination of oral diuretics based on furosemide, amiloride and hydrochlorothiazide is non-inferior to i.v. furosemide in weight control of patients with RNE and a similar safety profile.

Hypocomplementemic urticarial vasculitis syndrome (HUVS), or McDuffie syndrome, is a rare small vessel vasculitis associated with urticaria, hypocomplementemia and positivity of anti-C1q antibodies. In rare cases, HUVS can manifest as an immune-complex mediated glomerulonephritis with a membranoproliferative pattern of injury. Due to the rarity of this disorder, little is known about the clinical manifestation, pathogenesis, treatment response and outcome of such patients. We describe here three cases of HUVS with severe renal involvement. These patients had a rapidly progressive form of glomerulonephritis with severe nephrotic syndrome against a background of a membranoproliferative pattern of glomerular injury with extensive crescent formation. Therefore, these patients required aggressive induction and maintenance immunosuppressive therapy, with a clinical and renal response in two patients, while the third patient progressed to end-stage renal disease. Because of the rarity of this condition, there are few data regarding the clinical presentation, pathology and outcome of such patients. Accordingly, we provide an extensive literature review of cases reported from 1976 until 2020 and place them in the context of the current knowledge of HUVS pathogenesis. We identified 60 patients with HUVS and renal involvement that had adequate clinical data reported, out of which 52 patients underwent a percutaneous kidney biopsy. The most frequent renal manifestation was hematuria associated with proteinuria (70% of patients), while one third had abnormal kidney function on presentation (estimated glomerular filtration (GFR) below 60 mL/min/1.73 m²). The most frequent glomerular pattern of injury was membranoproliferative (35%), followed by mesangioproliferative (21%) and membranous (19%). Similar to other systemic vasculitis, renal involvement carries a poorer prognosis, but the outcome can be improved by aggressive immunosuppressive treatment.