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Background:Although most patients with atypical hemolytic uremic syndrome (aHUS) have variants in genes participating in alternative complement pathways, rare variants in non-complement pathway-related genes, including DGKE, INF2, MMACHC, PLG,and THBD, have also been described. Case Presentation:We report an 18-year-old male patient with renal biopsy-proven chronic thrombotic microangiopathy that raised suspicion of aHUS. Whole-exome sequencing revealed a novel pathogenic homozygous MMACHCc.484G>T (p.Gly162Trp) variant. Subsequently, clinical and laboratory findings confirmed cobalamin C (Cbl C) deficiency. Also, homozygous missense c.1112C>T PLG(p.Thr371Ile) variant was detected (it had been reported as a variant of unknown significance). However, the low serum plasminogen (PLG) activity proved the pathogenicity of c.1112C>T. Hence, the patient was diagnosed with concurrent Cbl C and PLG deficiencies. Segregation analysis revealed that the mother and father had the same heterozygous PLGand MMACHCvariants. PLGvariants have generally been described in aHUS patients concomitant with complement gene variants in the literature; therefore, the association between aHUS and PLGvariants is controversial. The possible contribution of PLG deficiency to thrombotic microangiopathy was also discussed in this case. Conclusion:Non-complement-mediated aHUS is an exceptional disorder. A limited number of genes are involved in this entity. To our knowledge, this is the first aHUS patient diagnosed with both Cbl C and PLG deficiencies in the literature.

Background: Percutaneous kidney biopsy is a fundamental procedure in nephrology. Although pregnancy is not a contraindication, a careful risk–benefit assessment is mandatory in pregnancy. We aimed to evaluate safety and diagnostic accuracy of percutaneous kidney biopsy in pregnancy in a single-center retrospective study. Methods: Percutaneous kidney biopsy was performed in 19 pregnant patients. Demographics, estimated glomerular filtration rates, serum albumin levels, and proteinuria levels at the time of biopsy were evaluated. Biopsy-related complications, diagnoses, and treatments during the follow-up were analyzed. In addition, delivery success, preeclampsia, early delivery, low birth weight rates, and long-term outcomes of the patients were retrieved and analyzed. Results: Mean patient age was 27 (range 16–41) years. Median gestational week at kidney biopsy was 20th. All but one biopsies were diagnostic. Median gestational week of delivery was 35 (range 23–39) gestational weeks. Preterm delivery (< 37 gestational weeks) and low birth weight (< 2500 mg) occurred in 73.7% and 52.6% of cases, respectively. Median weight at birth was 2500 mg. The incidence of preeclampsia was 57.9%. Overall 89.5% of the children survived. Median post-biopsy follow-up was 64 months. Maternal mortality was not observed during the follow-up period. End stage kidney disease developed in one patient. The results of percutaneous kidney biopsy led to therapeutic decisions in 73.7% of cases. Conclusions: Although percutaneous kidney biopsy is not frequently performed during pregnancy, it is relatively safe and usually diagnostic, and may guide further follow-up. Graphical abstract:

Passenger lymphocyte syndrome (PLS) causes immune-mediated hemolysis in solid and bone marrow transplant recipients. Donor-derived antibodies against the recipient erythrocyte drive the pathogenesis. It is a rare entity in kidney transplantation, and most of the cases are self-limited.

Background: The aim of this study was to evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN). Methods: A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years, with a follow-up period ≥ 1 year or who showed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, with C4d and CD68 staining. Results: Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7–7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated with the intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021]. Conclusions: An increased number of macrophages in the glomerular and tubulointerstitial area may play a role in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.

Passenger lymphocyte syndrome (PLS) causes immune-mediated hemolysis in solid and bone marrow transplant recipients. Donor-derived antibodies against the recipient erythrocyte drive the pathogenesis. It is a rare entity in kidney transplantation, and most of the cases are self-limited.