Gitelman syndrome and in vitro fertilization-embryo transfer: advancing preconception care in nephrology.

We report a case of a pregnant patient with Gitelman syndrome (GS) who conceived by in vitro fertilization-embryo transfer (IVF-ET). A 39-year-old woman was referred for hypokalemia, with a serum potassium level of 2.2 mEq/L. She had difficulty conceiving spontaneously. Because of her age, her hypokalemia could be exacerbated by pregnancy. We provided preconception care and managed her pregnancy by frozen-thawed embryo transfer with careful monitoring of the K levels. However, her serum K level dropped to 2.5 mEq/L at 8 weeks of gestation. It was expected that her K demand would increase with pregnancy; hence, she required hospitalization and a 1.5-fold increase in replacement dose to maintain her K levels. At 11 weeks of gestation, her serum K level rose to 3.0 mEq/L. The baby was born adequately sized after 38 weeks of gestation via vaginal delivery. The patient's K levels were stable during the postpartum period. Genetic testing revealed three heterozygous missense variants in SLC12A3 that were consistent with GS. In conclusion, preconception care and cooperation between internal medicine and obstetrics led to an excellent and successful delivery of an IVF fetus in an older patient with GS. There are no guidelines for electrolyte disorders in pregnancy, and only a few studies have reported on GS during pregnancy, including detailed postpartum assessments.

Kidney Biopsy Proven Thrombotic Microangiopathy Induced by Methamphetamine: A Case Report.

A 47-year-old man was admitted to our hospital with acute kidney injury, severe hypertension, heart failure, thrombocytopenia, and elevated lactate dehydrogenase. Renal biopsy revealed fibrin thrombi within the glomerular capillaries and moderate fibrotic intimal thickening in the interlobular arteries. The histological diagnosis was thrombotic microangiopathy (TMA). Regarding cardiac involvement, we found marked stenosis in the left anterior descending artery on coronary angiography and cardiomyopathy on myocardial biopsy. Blood concentrations of amphetamine and methamphetamine were high (14.1 ng/mL and 333 ng/mL, respectively). It is important to consider methamphetamine as a cause of renal TMA and multi-organ dysfunction.

Clinical features of women with thrombotic microangiopathy in pregnancy: A case series from a single Japanese tertiary perinatal care center.

AIM: Although perinatal thrombotic microangiopathy has become increasingly understood, the racial characteristics of patients with this condition remain unclear. Herein, we report the characteristics of patients with perinatal thrombotic microangiopathy at a single institution in Japan. METHODS: We conducted a retrospective study over a 5-year period from January 1, 2017, to December 31, 2021, using the electronic medical records of pregnant women who delivered at the perinatal center of our hospital. We extracted the data of those who developed perinatal thrombotic microangiopathy and evaluated their characteristics at the time of disease onset, final diagnosis, and maternal and fetal outcomes. RESULTS: Of the 10 224 deliveries that occurred during the 5-year period, only seven patients (0.06%) had perinatal thrombotic microangiopathy. The median pre-pregnant body mass index was 18.65 kg/m2 (minimum 17.3 kg/m2 , maximum 20.7 kg/m2 ). More than half of the patients were conceived by in-vitro fertilization, and 42% these had twin deliveries. Four patients had a history of rheumatic disease. The other three patients without underlying diseases developed thrombotic microangiopathy with HELLP syndrome, and one patient transitioned to atypical hemolytic uremic syndrome. CONCLUSIONS: Based on low body mass index and in-vitro fertilization, which are characteristic of Japanese women, medical complications and twin pregnancies may be a risk for thrombotic microangiopathy. Additionally, depending on the cause of thrombotic microangiopathy, its timing and onset differed.

Infection-Related Cryoglobulinemic Glomerulonephritis with Serum Anti-Factor B Antibodies Identified and Staining for NAPlr/Plasmin Activity Due to Infective Endocarditis.

In this rare case of infection-related cryoglobulinemic glomerulonephritis with infective endocarditis, a 78-year-old male presented with an acute onset of fever and rapidly progressive glomerulonephritis. His blood culture results were positive for Cutibacterium modestum, and transesophageal echocardiography showed vegetation. He was diagnosed with endocarditis. His serum immunoglobulin M, IgM-cryoglobulin, and proteinase-3-anti-neutrophil cytoplasmic antibody levels were elevated, and his serum complement 3 (C3) and C4 levels were decreased. Renal biopsy results showed endocapillary proliferation, mesangial cell proliferation, and no necrotizing lesions on light microscopy, with strong positive staining for IgM, C3, and C1q in the capillary wall. Electron microscopy showed deposits in the mesangial area in the form of fibrous structures without any humps. Histological examination confirmed a diagnosis of cryoglobulinemic glomerulonephritis. Further examination showed the presence of serum anti-factor B antibodies and positive staining for nephritis-associated plasmin receptor and plasmin activity in the glomeruli, suggesting infective endocarditis-induced cryoglobulinemic glomerulonephritis.

Intraoperative hemodialysis during open-heart surgery in patients with severe chronic kidney disease: a retrospective cohort study.

BACKGROUND: Acute kidney injury and chronic kidney disease (CKD) after cardiac surgery are associated with poor renal prognosis and increased mortality. The impact of intraoperative hemodialysis (IHD) on postoperative renal function remains unknown. We aimed to evaluate the utility of IHD during open-heart surgery in patients with severe non-dialysis-dependent chronic kidney disease (CKD-NDD) and its association with clinical outcomes. METHODS: This was a single-center retrospective cohort study that employed IHD during non-emergency open-heart surgery in patients with CKD stage G4 or G5. Patients who underwent emergent surgery, chronic dialysis, and/or kidney transplantation were excluded. We retrospectively compared the clinical characteristics and outcomes between patients from the IHD and non-IHD groups. The primary outcomes were 90-day mortality and postoperative initiation of renal replacement therapy (RRT). RESULTS: Twenty-eight patients were categorized into the IHD group and 33 into the non-IHD group. When comparing the IHD and non-IHD groups, men accounted for 60.7 vs. 50.3% of patients, the mean patient age was 74.5 (standard deviation [SD] 7.0) vs. 72.9 (SD 9.4) years (p = 0.744), and the proportion of patients with CKD G4 was 67.9 vs. 84.9% (p = 0.138). Regarding clinical outcomes, no significant differences were observed in the 90-day mortality (7.1 vs. 3.0%; p = 0.482) and 30-day RRT (17.9 vs. 30.3%; p = 0.373) rates between the groups. Among the patients with CKD G4, the IHD group had significantly lower 30-day RRT rates than the non-IHD group (0 vs. 25.0%; p = 0.032). RRT initiation was less likely for patients with CKD G4 (odds ratio 0.07, 95% confidence interval [CI] 0.01-0.37; p = 0.002); however, IHD did not significantly decrease the incidence of poor clinical outcomes (odds ratio 0.20, 95% CI 0.04-1.07; p = 0.061). CONCLUSIONS: IHD during open-heart surgery in patients with CKD-NDD did not improve their clinical outcomes with regards to postoperative dialysis. However, for patients with CKD G4, IHD may be useful for postoperative cardiac management.

Impact of ABO Compatibility/Incompatibility on the Perioperative Anti-SARS-CoV-2 Immunoglobulin G Levels in 2 Preoperatively Vaccinated Patients Undergoing Kidney Transplant: A Case Report.

Herein, we monitored the perioperative anti-SARS-CoV-2 spike immunoglobulin G titers in patients who were preoperatively vaccinated with 2 doses of a COVID-19 messenger RNA vaccine. Additionally, we compared the clinical settings between ABO-incompatible and ABO-compatible pre-emptive kidney transplant (KTx). Case 1 was of a 45-year-old man who was an ABO-incompatible KTx recipient. Before transplant, his serum antibody titers decreased from 278 U/mL at baseline to 41.9 U/mL after desensitization therapy (84.9% lower) and 54.7 U/mL (80.3% lower) at day 8; it is now maintained at 4.1 U/mL at 6 months posttransplant (98.5% lower). Case 2 was of a 50-year-old man who was an ABO-compatible KTx recipient. His serum antibody titer level decreased from 786 U/mL at baseline to 386 U/mL on day 8 (50.8% lower) and is now maintained at 156 U/mL at 6 months posttransplant (80.1% lower). We suggest that anti-SARS-CoV-2 spike immunoglobulin G titers should be monitored during the perioperative period to determine the optimal timing of COVID-19 vaccine booster doses for the maintenance of protective immunity, particularly in ABO-incompatible KTx recipients who require desensitization therapy.

Evaluation of the Correlation Between Responders and Non-Responders to the Second Coronavirus Disease Vaccination In Kidney Transplant Recipients: A Retrospective Single-Center Cohort Study.

BACKGROUND: The immune response to COVID-19 vaccination in kidney transplant (KTx) recipients is significantly lower than that in healthy controls. We evaluated immune responses after the COVID-19 vaccine and their possible relationship with other cofactors in KTx recipients. METHODS: This retrospective single-center cohort study included 29 KTx recipients 2-8 weeks after receiving 2 doses of the Pfizer-BioNTech SARS-CoV-2 messenger RNA vaccine. Anti-SARS-CoV-2 spike (S) immunoglobulin (Ig)-G levels were evaluated to define cofactors influencing the immune response between the responder (anti-SARS-CoV-2 IgG level ≥0.8 U/mL) (n = 16) and nonresponder groups (anti-SARS-CoV-2 IgG level <0.8 U/mL) (n = 13). The kinetics of antibodies between 2 and 6 months after the second vaccination was also compared between the groups. RESULTS: KTx recipients with IgG levels ≥0.8 U/mL were younger (54 [interquartile range {IQR}, 46.5-61] years vs 65 [IQR, 55-71.5] years; P = .01), had been transplanted for a longer median time (1588 [IQR, 1382-4751] days vs 1034 [IQR, 548.5-1833] days; P = .02), and were more often treated with a lower mycophenolate mofetil dosage (765.6 ± 119.6 vs 1077 ± 76.9 mg; P = .04) than KTx recipients with IgG levels <0.8 U/mL. There was no significant difference in antibody titers between time periods after the second dose in the responder group. At the 6-month follow-up, a serologic response against the SARS-CoV-2 S was observed in 44.4% of KTx recipients in the nonresponder group. CONCLUSIONS: More than 50% of KTx recipients developed a higher antibody response after the second dose of COVID-19 vaccination.

Comparison of antibody response following the second dose of SARS-CoV-2 mRNA vaccine in elderly patients with late-stage chronic kidney disease.

Background: Currently, it is unclear whether the progression of chronic kidney disease (CKD) could be an independent predictor of antibody response after administration of a COVID-19 vaccine. This study aimed to investigate the immune response to COVID-19 vaccination in patients with CKD stage G4 to G5 without renal replacement therapy and G5D using the recommended dose and schedule. Methods: This retrospective single-center cohort study evaluated immunogenicity regarding antibody response after COVID-19 vaccination in our hospital for late-stage CKD patients aged ≥ 60 years. We evaluated antibody responses in 48 patients with CKD G4, 35 patients with CKD G5, and 70 patients undergoing hemodialysis (HD; CKD G5D). Results: After the second vaccination, anti-SARS-CoV-2-S (Spike) IgG levels were found to be positive (> 0.8 U/mL) in all CKD G4 and G5 patients (100%), and 69 of 70 HD patients (98.5%). The median (interquartile range [IQR] S-IgG level (Ab titers) was 358 [130.2-639.2], 218 [117-377], and 185.5 [95.1-323.5] U/mL in the CKD G4, G5, and HD groups, respectively. The median S-IgG levels were significantly lower in the HD group than in the CKD G4 group (p < 0.01). However, there was no significant difference in the antibody titers between the CKD G4 and G5 groups. To further analyze the decline in S-IgG levels after 6 months, we additionally assessed and compared antibody titers at 1 month and 6 months after the second vaccination in the HD group. Compared with the median S-IgG levels of 185.5 [95.1-323.5] U/mL 1 month after the second dose, the median S-IgG level 6 months thereafter was significantly decreased at 97.4 [62.5-205.5] U/mL (p < 0.05). Conclusions: We highlight two major factors of variability in the vaccine response. First, in elderly patients with late-stage CKD, antibody titers tended to be lower in the G5D group than in the G4 and G5 groups despite the shorter time since vaccination; therefore, CKD stage progression might cause a decline in antibody titers. Second, waning immune responses were observed 6 months after second dose administration in HD patients advocating a potential need for a third booster dose vaccine after 6 months.

Use of Immunosuppressive Therapy in the Treatment of IgA-dominant Infection-related Glomerulonephritis.

A 51-year-old Japanese man who experienced colon cancer recurrence following primary and metastatic lesion resection was hospitalized due to facial cellulitis with febrile neutropenia and purpura on his lower extremities after chemotherapy. It was complicated by rapidly progressive glomerulonephritis. He was diagnosed with immunoglobulin A (IgA)-dominant endocapillary proliferative glomerulonephritis based on kidney histology. His glomeruli were positive for the nephritis-associated plasmin receptor, plasmin activity and galactose-deficient IgA1 (Gd-IgA1). A skin biopsy immunofluorescence study revealed IgA deposition within perivascular regions but no Gd-IgA1 deposition. The final diagnosis was IgA-dominant infection-related glomerulonephritis (IRGN). The patient's renal function returned to normal after receiving immunosuppressive therapy that consisted of a glucocorticoid and a cyclophosphamide. Immunosuppressive therapy should be considered in cases of IRGN if the patient's infection is completely under control.