Kidney transplantation in multiple myeloma in 2023: A short review.

Patients with multiple myeloma (MM) frequently present with kidney involvement, of which a non-negligible proportion will progress to end-stage kidney disease. Kidney transplantation (KT) is the preferred kidney replacement therapy for selected patients; however, there are still many uncertainties regarding its application in MM patients. The risk of hematological relapse and subsequent graft loss or patient death often leads nephrologists to deem these patients unfit for KT. As such, data on KT in MM patients are heterogeneous and originate from individual case reports and small case series. Although MM is still an incurable disease, the addition of newer drugs and autologous hematopoietic stem cell transplant (HSCT) in the standard of care has been increasing patients' overall survival in recent decades. Risk stratification using cytogenetic studies and minimal residual disease detection are helpful in assessing the risk of relapse in patients who attain a complete response after HSCT. The greatest challenges remain the correct identification of patients who will most probably benefit from KT from a survival perspective and the determination of how long relapse-free survival should be before the transplant is performed.

Eculizumab discontinuation in a patient with atypical hemolytic uremic syndrome after ChAdOx1 nCoV-19 vaccination.

Eculizumab has proven to be effective in patients with atypical hemolytic uremic syndrome (aHUS) in clinical trials and in the real world, but the optimal duration of therapy remains unknown. Standard maintenance treatment is often life-long, but the possibility of discontinuation has not yet been systematically tested. We describe a case of aHUS after ChAdOx1 nCoV-19 vaccination in a patient with homozygous CFHR3/CFHR1 gene deletion who discontinued eculizumab maintenance therapy 24 weeks after achieving disease remission. We report the safety of discontinuing eculizumab treatment with the aim of minimizing the risk of adverse reactions, reducing the risk of meningitis, improving quality of life, and reducing the considerable treatment costs.

Efficiency of ferric carboxymaltose in non-dialysis CKD patients and its impact on kidney function: a prospective observational study.

BACKGROUND: Iron deficiency anemia occurs in most patients with non-dialysis chronic kidney disease (ND-CKD). Previous studies have suggested that intravenous (IV) iron therapy is more effective than oral iron in these patients. Clinical evidence relating the effects of IV iron on renal function is, however, limited. METHODS: Prospective observational study of adult patients with ND-CKD, anemia, iron deficiency, and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, treated with a single dose of 500 mg or 1000 mg of ferric carboxymaltose (FCM) and followed-up for 24 weeks. Primary outcome was FCM efficacy, assessed by comparing Hb, TSAT and ferritin at 24 weeks with those at baseline. Secondary outcome was FCM impact on renal function, evaluated by comparing eGFR over the same period. RESULTS: One hundred and forty patients were recruited: seventy-eight (55.7%) were treated with 1000 mg and 62 (44.3%) with 500 mg of FCM. 24 weeks after FCM administration, Hb increased 1.54 ± 1.99 g/dL (95% CI 1.09-1.99, p = 001) in the group treated with 1000 mg and 0.86 ± 1.4 g/dL (95% CI 0.53-1.22, p = 0.001) in those treated with 500 mg. TSAT increased in both groups but more in those treated with 1000 mg, and ferritin only increased in the latter. Estimated GFR showed a significant increase of 1.55 ± 6.86 mL/min/m2 (95% CI 0.05-3.09, p = 0.049), from a baseline of 27.73 ± 17.23 to 28.88 ± 18.02 mL/min/m2 in the group treated with 1000 mg. CONCLUSIONS: Our findings suggested that IV FCM therapy was effective in improving serum iron levels and anemia in ND-CKD stage 3 to 5 patients. Higher doses seem to be necessary to replace depleted iron stores. In our cohort, IV FCM therapy was associated with an improvement in renal function, particularly in those treated with higher doses of FCM.

Vascular access type and mortality in elderly incident hemodialysis patients.

INTRODUCTION: The ideal vascular access type for elderly hemodialysis (HD) patients remains debatable. The aim of this study was to analyze the association between patterns of vascular access use within the first year of HD and mortality in elderly patients. METHODS: Single-center retrospective study of 99 incident HD patients aged≥80 years from January 2010 to May 2021. Patients were categorized according to their patterns of vascular access use within the first year of HD: central venous catheter (CVC) only, CVC to arteriovenous fistula (AVF), AVF to CVC, and AVF only. Baseline clinical data were compared among groups. Survival outcomes were analyzed using Kaplan-Meier survival curves and Cox's proportional hazards model. RESULTS: When compared with CVC to AVF, mortality risk was significantly higher among CVC only patients and similar to AVF only group [HR 0.93 (95% CI 0.32-2.51)]. Ischemic heart disease [HR 1.74 (95% CI 1.02-2.96)], lower levels of albumin [HR 2.16 (95% CI 1.28-3.64)] and hemoglobin [HR 4.10(95% CI 1.69-9.92)], and higher levels of c-reactive protein [HR 1.87(95% CI 1.11-3.14)] were also associated with increased mortality risk in our cohort, p<0.05. CONCLUSION: Our findings suggested that placement of an AVF during the early stages of dialysis was associated with lower mortality compared to persistent CVC use among elderly patients. AVF placement appears to have a positive impact on survival outcomes, even in those who started dialysis with a CVC.

Minimal change disease and COVID-19 vaccination: Four cases and review of literature.

There have been multiple reports of the development of de novo or relapse of glomerular diseases after SARS-CoV-2 vaccination. While most of them have occurred with the mRNA vaccines (Pfizer/BioNTech and Moderna/NIAID), there also have been reports associated with the vector vaccines (AstraZeneca/ChAdOx1-S) vaccine and the inactivated vaccines. Minimal change disease (MCD) is one of the more common glomerular diseases noted to have been associated with the COVID-19 vaccination. We report here 4 more cases of MCD occurring in association with the COVID-19 vaccine, 3 were de novo cases, and 1 case had a relapse of MCD. We also review all the 41 cases described thus far in the literature and review potential common pathways activated by the vaccination that play a role in the pathogenesis of MCD.

Central Diabetes Insipidus Following Immunization With BNT162b2 mRNA COVID-19 Vaccine: A Case Report.

Introduction: Cases of central diabetes insipidus (CDI) have been reported after COVID-19 infection, with hypophysitis being the most likely cause. COVID-19 vaccines potential adverse effects may mimetize some of these complications. Case Report: Woman 37 years old, with rheumatoid arthritis under adalimumab (40 mg twice a month) since December 2018. She was in her usual state of health when she has received the second dose of BNT162b2 mRNA COVID-19 vaccine (June 2021). Seven days later, she started reporting intense thirst and polyuria and consulted her family physician. Blood Analysis: creatinine 0.7 mg/dL, glucose 95mg/dL, Na+ 141mEq/L, K+ 3.9 mEq/L, TSH 3.8 mcUI/L (0.38-5.33), FT4 0.9 ng/dL (0.6-1.1), cortisol 215.4 nmol/L (185-624), ACTH 21.9 pg/mL (6- 48), FSH 4.76 UI/L, LH5.62 UI/L, estradiol 323 pmol/L, IGF1 74.8 ng/mL (88-209), PRL 24.7mcg/L (3.3-26.7) osmolality 298.2 mOs/Kg (250- 325); Urine analysis: volume 10200 mL/24h, osmolality 75 mOs/Kg (300-900), density 1.002. On water restriction test: 0' - Serum osmolality 308.8mOsm/Kg vs. urine osmolality 61.0 mOsm/Kg; 60' - urine osmolality 102 mOsm/Kg; urine osmolality 1 h after desmopressine was 511mOsm/kg. MRI revealed no abnormal signs consistent with hypophysitis except for the loss of the posterior pituitary bright spot on T1 weighted imaging. Diagnosis of CDI was assumed, and started therapy with desmopressine. A report of potential adverse effect was addressed to national health authorities. Conclusion: In hypophysitis MRI often shows loss of posterior pituitary bright spot on T1 weighted imaging, pituitary enlargement or stalk thickening but those findings were not present in this patient. To the best of our knowledge, CDI has never been reported following administration of a COVID-19 vaccine.

Atypical Hemolytic Uremic Syndrome after ChAdOx1 nCoV-19 Vaccination in a Patient with Homozygous CFHR3/CFHR1 Gene Deletion.

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA) affecting the kidneys. Compared with typical HUS due to an infection from shiga toxin-producing Escherichia coli, atypical HUS involves a genetic or acquired dysregulation of the complement alternative pathway. In the presence of a mutation in a complement gene, a second trigger is often necessary for the development of the disease. We report a case of a 54-year-old female, with a past medical history of pulmonary tuberculosis, who was admitted to the emergency service with general malaise and reduction in urine output, 5 days after vaccination with ChAdOx1 nCoV-19. Laboratory results revealed microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given the clinical picture of TMA, plasma exchange (PEX) was immediately started, along with hemodialysis. Complementary laboratory workup for TMA excluded thrombotic thrombocytopenic purpura and secondary causes. Complement study revealed normal levels of factors H, B, and I, normal activity of the alternate pathway, and absence of anti-factor H antibodies. Genetic study of complement did not show pathogenic variants in the 12 genes analyzed, but revealed a deletion in gene CFHR3/CFHR1 in homozygosity. Our patient completed 10 sessions of PEX, followed by eculizumab, with both clinical and laboratorial improvement. Actually, given the short time lapse between vaccination with ChAdOx1 nCoV-19 and the clinical manifestations, we believe that vaccine was the trigger for the presentation of aHUS in this particular case.

Humoral response to BNT162b2 mRNA COVID-19 vaccine in peritoneal and hemodialysis patients: A comparative study.

INTRODUCTION: Maintenance dialysis patients (MDP) are at higher risk of exposure with increased mortality from COVID-19 with generalized immunization becoming the cornerstone in prevention. This study aims to compare humoral response between hemodialysis (HD) and peritoneal dialysis (PD) patients. MATERIALS AND METHODS: Observational prospective study following HD and PD programs from a Portuguese Center receiving BNT162b2 vaccine. Specific anti-Spike IgG quantification to compare both for absolute value and non-responders (NR) between modalities and against risk factors. RESULTS: Of 67 MDP, 42 were HD and 25 PD patients. PD developed higher antibody titers after both first (median 5.44 vs. 0.99 AU/ml, p < 0.01) and second dose (median 170.43 vs. 65.81 AU/ml; p < 0.01). HD associated with NR after the first dose (p < 0.01). CONCLUSION: This study demonstrated improved humoral immunogenicity with BNT162b2 in PD compared to HD patients. These differences are attributed to comorbidity burden and age differences, rather than dialysis modality.

Hypertension-associated thrombotic microangiopathy in an adult patient with complement factor H autoantibodies and a rare heterozygous variant in the CFH gene.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal injury, which results from thrombotic microangiopathy (TMA) within the glomerular capillaries and arterioles. We report a case of a biopsy-proven renal TMA attributed to hypertension in a 42-year-old woman with undiagnosed alternative complement pathway dysregulation resulting from a rare association between complement factor H (CFH) autoantibodies and a heterozygous variant in the CFH gene. We propose that severe hypertension triggered an over-activation of the alternative complement pathway in a patient with genetic predisposition. In this case, blood pressure control allowed normalization of hematologic parameters and partial recovery of renal function, supporting the idea that shear stress is an important complement-amplifying factor.