Renal hypomagnesemia syndromes involving CNNM2 protein pathogenic variants are associated with variable degrees of neurocognitive dysfunction and hypomagnesemia. Here, we report a family with a novel CNNM2 p.Pro482Ala variant, presenting with overt hypomagnesemia and mild neurological involvement (autosomal dominant renal hypomagnesemia 6, HOMG6, MIM# 613882). Using a bioinformatics approach, we showed that the p.Pro482Ala amino acid substitution causes a 3D conformational change in CNNM2 structure in the cystathionin beta synthase (CBS) domain and the carboxy-terminal protein segment. A novel finding was that aldosterone inhibition with spironolactone helped to alleviate hypomagnesemia and symptoms in the proband.

The evolving landscape of clinical genetics is becoming increasingly relevant in the field of nephrology. HNF1B-associated renal disease presents with a diverse array of renal and extrarenal manifestations, prominently featuring cystic kidney disease and diabetes mellitus. For the genetic analyses, whole exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) were performed. Bioinformatics analysis was performed with Ingenuity Clinical Insights software (Qiagen). The patient’s electronic record was utilized after receiving informed consent. In this report, we present seven cases of HNF1B-associated kidney disease, each featuring distinct genetic abnormalities and displaying diverse extrarenal manifestations. Over 12 years, the mean decline in eGFR averaged −2.22 ± 0.7 mL/min/1.73 m². Diabetes mellitus was present in five patients, kidney dysplastic lesions in six patients, pancreatic dysplasia, hypomagnesemia and abnormal liver function tests in three patients each. This case series emphasizes the phenotypic variability and the fast decline in kidney function associated with HNF-1B-related disease. Additionally, it underscores that complex clinical presentations may have a retrospectively straightforward explanation through the use of diverse genetic analytical tools.

Given the high cardiovascular risk accompanying end-stage kidney disease, it would be of paramount importance for the clinical nephrologist to know which screening method(s) identify high-risk patients and whether screening asymptomatic transplant candidates effectively reduces cardiovascular risk in the perioperative setting as well as in the longer term. Within this review, key studies concerning the above questions are reported and critically analyzed. The lack of unified screening criteria and of a prognostically sufficient screening cardiovascular effect for renal transplant candidates sets the foundation for a personalized patient approach in the near future and highlights the need for well-designed studies to produce robust evidence which will address the above questions.

Background: The relative merits of the Henderson–Hasselbalch (HH) versus Stewart frameworks for interpreting dialysis-associated acid–base shifts remain debated. Dialysis alters systemic pH through exogenous bicarbonate delivery, chloride displacement, and removal of organic anions. We compared these approaches across hemodialysis (HD) and peritoneal dialysis (PD). Methods: We studied 53 HD patients with paired pre/post-HD blood gas and chemistry (106 observations) and 41 PD patients cross-sectionally, totaling 147 datasets. Derived variables followed the Figge/Stewart implementation [apparent SID (SIDa), effective SID (SIDe), strong ion gap (SIG), albumin-corrected anion gap (AGc)]. For HD, changes in pH (ΔpH) were modeled using HH predictors (ΔHCO₃⁻, ΔPCO₂) and Stewart predictors (ΔSIDa, ΔATOT, ΔPCO₂). For cross-sectional data (pre-HD, post-HD, and PD), HH- and Stewart-based level models were fitted. Stewart-predicted pH was also computed using the Figge and the simplified Constable electroneutrality equation. Results: HD increased pH by 0.11, driven by ΔHCO₃⁻ = +5.7 mΕq/L, ΔCl⁻ = −2.3 mEq/L, and declines in unmeasured anions (ΔSIG = −3.9; ΔAGc = −3.3). SIDa increased only marginally (+1.3 mEq/L), whereas SIDe rose by +5.3 mEq/L and fully tracked the alkalinization. In Δ-models, HH explained 90% of variance in ΔpH (R² = 0.903) compared with 51% for Stewart (R² = 0.514). In level models, HH explained 96% of pH variance versus 36% for Stewart. Bland–Altman analysis showed systematic overestimation of pH by the Figge and Constable approach (bias + 0.111), most pronounced pre-HD. PD patients had consistently higher AGc and SIG values than HD patients, indicating a greater burden of unmeasured anions. Conclusions: Alkalinization during HD is primarily attributable to bicarbonate gain, chloride displacement, and organic-anion clearance. The HH framework provides superior predictive performance for ΔpH, while closed-system Stewart formulations based on SIDa underestimate alkalinization. However, a broader physicochemical interpretation using SIDe and SIG, which incorporate bicarbonate and unmeasured anions, coherently describes the observed physiology. Future applications of the Stewart approach in dialysis should emphasize SIDe and SIG to better reflect the open-system physiology of both HD and PD. Our findings suggest that the HH model remains more predictive of alkalinization, while SIDe and SIG refine the physicochemical understanding.

BACKGROUND Transplantation using kidneys from older donors or those with specific risk factors (marginal kidneys) offers improved outcomes compared to remaining on dialysis. Matched-pair analysis potentiates control for confounding donor factors and the impact of recipient characteristics on transplant survival. MATERIAL AND METHODS Data from 200 transplants using marginal deceased donors were retrospectively analyzed. Paired comparisons between mate kidney recipients, McNemar's test, and multivariable Cox regression were performed to identify recipient factors and histological features from zero-time biopsy associated with graft survival. RESULTS Graft survival was significantly longer in recipients with shorter pre-transplant dialysis exposure (mean 58.10 vs 68.86 months, P=0.001) and fewer HLA mismatches (3.40 vs 3.78, P=0.013). Severe acute tubular injury (ATI) in pre-implantation biopsy was associated with reduced graft survival (P=0.04). In multivariable Cox regression, the presence of severe ATI (P<0.001), older recipient age (HR=0.1 per year, P=0.002), HLA mismatches (HR=1.21, P=0.011), and elevated 1-year serum creatinine level (HR=0.72, P=0.030) remained independently associated with shorter graft survival. CONCLUSIONS Matched-pair analysis and multivariable modelling identified recipient dialysis duration, age, HLA mismatches,1-year serum creatinine, and pre-transplant biopsy findings, particularly severe ATI, as key predictors of graft survival in marginal kidney transplantation. These insights may support improved recipient selection and post-transplant management of marginal-donor kidneys.

Background: Nephrogenic diabetes insipidus (NDI) is a rare disorder characterized by renal resistance to arginine vasopressin, most commonly caused by pathogenic variants in the AVPR2 gene. While X-linked NDI classically affects males, heterozygous females may exhibit variable clinical expression. Certain AVPR2 variants are associated with partial NDI and milder phenotypes. Methods: We conducted a retrospective family study of a multigenerational Greek pedigree with suspected hereditary NDI. Clinical, biochemical, and pedigree data were collected through chart review and family interviews. Genetic analysis was performed using whole-exome sequencing, and variant interpretation followed ACMG/AMP guidelines. Results: Fourteen individuals across four generations were evaluated. Molecular analysis identified a familial AVPR2 (NM_000054.7):c.964C>T (p.Pro322Ser) missense variant in three males and three females, with obligate carrier status inferred in two deceased females, segregating in an X-linked pattern. Hemizygous males exhibited a broad phenotypic spectrum, ranging from partial NDI with later onset to severe early-onset disease with urinary tract complications. Heterozygous females showed variable expression, from asymptomatic carriers to mildly symptomatic individuals. The variant co-segregated with disease and, based on ACMG criteria, it was classified as pathogenic. Conclusions: In our family, the AVPR2 c.964C>T (p.Pro322Ser) variant was associated with a remarkably broad clinical spectrum, ranging from asymptomatic heterozygous females to severe early-onset disease with urinary tract complications in affected males. These observations emphasize the need for early molecular diagnosis, systematic evaluation of female carriers, and long-term surveillance to prevent disease-related complications and optimize genetic counselling.