IntroductionAtypical hemolytic uremic syndrome (aHUS) is associated with rapid progression to end-stage renal disease (ESRD). In undiagnosed cases of aHUS, post-transplant recurrence is a nightmare. Thus, pre-transplant diagnosis of aHUS should be sought in suspected cases. In this series, we present two aHUS cases and one complement-related glomerulopathy (CRG), who underwent live-related renal transplantation with the mother as a donor having similar genetic mutations.MethodsPersistent blood pressure (BP) elevation, borderline thrombocytopenia, and previous unknown cause of renal disease prompted us to evaluate aHUS or CRG. aHUS was diagnosed with anti-factor H (AFH) antibody levels >100 Au/ml. Patients who had AFH levels <100 AU/ml but had genetic mutations in the complement factor H (CFH) or CFH related proteins (CFHR) were considered as complement-related glomerulopathy (CRG). We identified the clinical and outcome data of such three patients from our electronic database and presented it here.ResultsThe first case is of a 25-year-old male with hypertension, bilateral small size kidneys with the basic renal disease being unknown was on hemodialysis for ESRD for 9 months. Pretransplant workup revealed anemia, normal lactate dehydrogenase (LDH), and borderline low platelet counts. He underwent a renal transplant with his mother as a donor. Immediate post-transplant, he had slow creatinine clearance from day 3 to day 5 with falling platelet counts and rising LDH levels. With a suspicion of tacrolimus induced HUS, he was shifted to cyclosporine. However, even till day 7, creatinine clearance was slow. With a strong clinical suspicion of underlying aHUS now, we assessed AFH levels that were elevated (276.01 AU/ml). Genetic analysis revealed homozygous deletion in complement factor H related protein 1 (CFHR 1, exon 5,6 and intron 1,3), and CFHR 3 (exon 1,2,3,6 and intron 4). He received 5 sessions of plasma exchange (PE), 2 doses of rituximab (500 mg x 2 weeks) and 4 doses of bortezomib (2 mg). Repeat AFH levels at the end of PE were normalized (<60 AU/ml). Nine months post-transplant, his creatinine is stable with a value of 1.62 mg/dl, BP controlled with a single antihypertensive drug with normal hemoglobin and LDH levels.Another case is of a 22-year-old male with ESRD who was diagnosed with aHUS before transplant. His AFH level was 383.5 AU/ml. Similarly, a 45-year-old male was diagnosed with complement-related glomerulopathy (CRG). His AFH levels were 92 AU/ml. Genetic analysis revealed duplication in CFHR 3 (upstream region, exons 1, 2, 3, 6, and intron 4), CFHR 1 (intron 3 and exons 5, 6) in both cases. Pre-transplant, patients received six and five cycles of PE, two doses of rituximab (500 mg) two weeks apart, and intravenous immunoglobulin (total dose 5 gm). The AFH levels decreased to 61 AU/ml in both patients from higher baseline values. At nine- and five-months follow-up post-transplant, both have functioning grafts with serum creatinine levels of 1.72 mg/dl and 1.97 mg/dl.ConclusionsA strong clinical suspicion of aHUS or CRG is necessary for young hypertensive patients with anemia and renal dysfunction. Renal transplant in AFH antibody-positive aHUS cases can be considered after due explanation of recurrence with the use of pretransplant PE and rituximab after documenting normal AFH levels.No conflict of interest IntroductionAtypical hemolytic uremic syndrome (aHUS) is associated with rapid progression to end-stage renal disease (ESRD). In undiagnosed cases of aHUS, post-transplant recurrence is a nightmare. Thus, pre-transplant diagnosis of aHUS should be sought in suspected cases. In this series, we present two aHUS cases and one complement-related glomerulopathy (CRG), who underwent live-related renal transplantation with the mother as a donor having similar genetic mutations. Atypical hemolytic uremic syndrome (aHUS) is associated with rapid progression to end-stage renal disease (ESRD). In undiagnosed cases of aHUS, post-transplant recurrence is a nightmare. Thus, pre-transplant diagnosis of aHUS should be sought in suspected cases. In this series, we present two aHUS cases and one complement-related glomerulopathy (CRG), who underwent live-related renal transplantation with the mother as a donor having similar genetic mutations. MethodsPersistent blood pressure (BP) elevation, borderline thrombocytopenia, and previous unknown cause of renal disease prompted us to evaluate aHUS or CRG. aHUS was diagnosed with anti-factor H (AFH) antibody levels >100 Au/ml. Patients who had AFH levels <100 AU/ml but had genetic mutations in the complement factor H (CFH) or CFH related proteins (CFHR) were considered as complement-related glomerulopathy (CRG). We identified the clinical and outcome data of such three patients from our electronic database and presented it here. Persistent blood pressure (BP) elevation, borderline thrombocytopenia, and previous unknown cause of renal disease prompted us to evaluate aHUS or CRG. aHUS was diagnosed with anti-factor H (AFH) antibody levels >100 Au/ml. Patients who had AFH levels <100 AU/ml but had genetic mutations in the complement factor H (CFH) or CFH related proteins (CFHR) were considered as complement-related glomerulopathy (CRG). We identified the clinical and outcome data of such three patients from our electronic database and presented it here. ResultsThe first case is of a 25-year-old male with hypertension, bilateral small size kidneys with the basic renal disease being unknown was on hemodialysis for ESRD for 9 months. Pretransplant workup revealed anemia, normal lactate dehydrogenase (LDH), and borderline low platelet counts. He underwent a renal transplant with his mother as a donor. Immediate post-transplant, he had slow creatinine clearance from day 3 to day 5 with falling platelet counts and rising LDH levels. With a suspicion of tacrolimus induced HUS, he was shifted to cyclosporine. However, even till day 7, creatinine clearance was slow. With a strong clinical suspicion of underlying aHUS now, we assessed AFH levels that were elevated (276.01 AU/ml). Genetic analysis revealed homozygous deletion in complement factor H related protein 1 (CFHR 1, exon 5,6 and intron 1,3), and CFHR 3 (exon 1,2,3,6 and intron 4). He received 5 sessions of plasma exchange (PE), 2 doses of rituximab (500 mg x 2 weeks) and 4 doses of bortezomib (2 mg). Repeat AFH levels at the end of PE were normalized (<60 AU/ml). Nine months post-transplant, his creatinine is stable with a value of 1.62 mg/dl, BP controlled with a single antihypertensive drug with normal hemoglobin and LDH levels.Another case is of a 22-year-old male with ESRD who was diagnosed with aHUS before transplant. His AFH level was 383.5 AU/ml. Similarly, a 45-year-old male was diagnosed with complement-related glomerulopathy (CRG). His AFH levels were 92 AU/ml. Genetic analysis revealed duplication in CFHR 3 (upstream region, exons 1, 2, 3, 6, and intron 4), CFHR 1 (intron 3 and exons 5, 6) in both cases. Pre-transplant, patients received six and five cycles of PE, two doses of rituximab (500 mg) two weeks apart, and intravenous immunoglobulin (total dose 5 gm). The AFH levels decreased to 61 AU/ml in both patients from higher baseline values. At nine- and five-months follow-up post-transplant, both have functioning grafts with serum creatinine levels of 1.72 mg/dl and 1.97 mg/dl. The first case is of a 25-year-old male with hypertension, bilateral small size kidneys with the basic renal disease being unknown was on hemodialysis for ESRD for 9 months. Pretransplant workup revealed anemia, normal lactate dehydrogenase (LDH), and borderline low platelet counts. He underwent a renal transplant with his mother as a donor. Immediate post-transplant, he had slow creatinine clearance from day 3 to day 5 with falling platelet counts and rising LDH levels. With a suspicion of tacrolimus induced HUS, he was shifted to cyclosporine. However, even till day 7, creatinine clearance was slow. With a strong clinical suspicion of underlying aHUS now, we assessed AFH levels that were elevated (276.01 AU/ml). Genetic analysis revealed homozygous deletion in complement factor H related protein 1 (CFHR 1, exon 5,6 and intron 1,3), and CFHR 3 (exon 1,2,3,6 and intron 4). He received 5 sessions of plasma exchange (PE), 2 doses of rituximab (500 mg x 2 weeks) and 4 doses of bortezomib (2 mg). Repeat AFH levels at the end of PE were normalized (<60 AU/ml). Nine months post-transplant, his creatinine is stable with a value of 1.62 mg/dl, BP controlled with a single antihypertensive drug with normal hemoglobin and LDH levels. Another case is of a 22-year-old male with ESRD who was diagnosed with aHUS before transplant. His AFH level was 383.5 AU/ml. Similarly, a 45-year-old male was diagnosed with complement-related glomerulopathy (CRG). His AFH levels were 92 AU/ml. Genetic analysis revealed duplication in CFHR 3 (upstream region, exons 1, 2, 3, 6, and intron 4), CFHR 1 (intron 3 and exons 5, 6) in both cases. Pre-transplant, patients received six and five cycles of PE, two doses of rituximab (500 mg) two weeks apart, and intravenous immunoglobulin (total dose 5 gm). The AFH levels decreased to 61 AU/ml in both patients from higher baseline values. At nine- and five-months follow-up post-transplant, both have functioning grafts with serum creatinine levels of 1.72 mg/dl and 1.97 mg/dl. ConclusionsA strong clinical suspicion of aHUS or CRG is necessary for young hypertensive patients with anemia and renal dysfunction. Renal transplant in AFH antibody-positive aHUS cases can be considered after due explanation of recurrence with the use of pretransplant PE and rituximab after documenting normal AFH levels.No conflict of interest A strong clinical suspicion of aHUS or CRG is necessary for young hypertensive patients with anemia and renal dysfunction. Renal transplant in AFH antibody-positive aHUS cases can be considered after due explanation of recurrence with the use of pretransplant PE and rituximab after documenting normal AFH levels.