Non-crystalline light chain proximal tubulopathy, a morphologically protean entity.

BACKGROUND: Light chain proximal tubulopathy (LCPT) is a rare form of paraprotein-related disease, occurring in two main histopathological forms: crystalline and non-crystalline. The clinicopathological features, treatment strategies and outcomes, especially of the non-crystalline form, are not well described. METHODS: We conducted a single-centre retrospective case series of 12 LCPT patients, 5 crystalline and 7 non-crystalline, between 2005 and 2021. RESULTS: The median age was 69.5 years (range 47-80). Ten patients presented with CKD and significant proteinuria (median estimated glomerular filtration rate of 43.5 ml/min/1.73 m2; urine protein:creatinine ratio 328 mg/mmol). Only six patients had known haematological disease at the time of renal biopsy. Multiple myeloma (MM) was diagnosed in seven patients cases and monoclonal gammopathy of renal significance (MGRS) in five patients. A clone was detected in all cases combining serum/urine electrophoresis and free light chain (LC) assays. Crystalline and non-crystalline variants had similar clinical presentations. For the non-crystalline variant, a diagnosis was reached based on a combination of CKD without another cause, haematological workup, LC restriction on immunofluorescence and abnormalities on electron microscopy (EM). Nine of 12 patients received clone-directed treatment. Patients who achieved haematological response (including all non-crystalline LCPT) had improved renal outcomes over a median follow-up of 79 months. CONCLUSIONS: The non-crystalline variant may go unrecognised because of its subtle histopathological features and requires EM to distinguish it from 'excessive LC resorption without tubular injury'. Clone-directed treatment with good haematological response improves renal outcomes in both variants but limited data exist in MGRS. Multicentre prospective studies are needed to better define the clinicopathological characteristics associated with poor outcomes and optimize treatment strategies in patients with MGRS.

Diagnosis of tuberculosis in dialysis and kidney transplant patients.

BACKGROUND AND OBJECTIVES: In patients with chronic kidney disease the risk of developing Tuberculosis is increased, while the presentation is often atypical making the diagnosis more difficult. The aim of this study is to describe the presentation of Tuberculosis in dialysis and kidney transplant patients, including the range of diagnostic approaches and the utility of different sample types. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: In this retrospective study, case records of dialysis and kidney transplant patients were reviewed, including all those treated for Tuberculosis between January 2009 and December 2020. RESULTS: Over 12 years, there were 143 cases of Tuberculosis in 141 patients (aged 17-86, 50.4% male). Tuberculosis was most common in Asian patients (64%) and those receiving hemodialysis (82%), particularly during the first year after dialysis initiation (54% of dialysis cases). Non-pleural/pulmonary disease accounted 40% of cases, and non-organ-specific presenting features were prominent including fever, lymphadenopathy, and weight loss. The diagnosis was confirmed microbiologically or histologically in 87 cases (61%), with low sensitivity observed for many types of samples including sputum (18%) and pleural fluid (12%). Higher sensitivity was observed with tissue samples including bronchoscopic lymph node aspiration (75%) and other lymph node sampling (92%). In the 52 cases where drug sensitivities were available, resistance to a first line treatment, most commonly isoniazid, was seen in 12 cases (23%). Furthermore, 1- and 5-year survival from diagnosis were 78% and 61%, respectively. Baseline variables independently associated with poorer survival were age (OR 1.8 per decade, 95% CI 1.4-2.3), weight loss over 10% (OR 1.9, 95% CI 1.0-3.5), and a non-confirmed diagnosis (OR 1.6, 95% CI 1.2-2.1). CONCLUSIONS: Tuberculosis is common in dialysis and kidney transplant patients, particularly during the first year of dialysis. Short-term mortality is high, but the diagnostic sensitivity of many types of samples is low, so that diagnosis is difficult, with treatment often initiated without confirmation. These data highlight the importance of judgment and clinical experience with this complex patient group.

Longevity of SARS-CoV-2 immune responses in hemodialysis patients and protection against reinfection.

Patients with end stage kidney disease receiving in-center hemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, patients receiving ICHD frequently develop circulating antibodies to SARS-CoV-2, even with asymptomatic infection. Here, we investigated the durability and functionality of the immune responses to SARS-CoV-2 infection in patients receiving ICHD. Three hundred and fifty-six such patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection. Patients were regularly screened for nucleocapsid protein (anti-NP) and receptor binding domain (anti-RBD) antibodies, and those who became seronegative at six months were screened for SARS-CoV-2 specific T-cell responses. One hundred and twenty-nine (36.2%) patients had detectable antibody to anti-NP at time zero, of whom 127 also had detectable anti-RBD. Significantly, at six months, 71/111 (64.0%) and 99/116 (85.3%) remained anti-NP and anti-RBD seropositive, respectively. For patients who retained antibody, both anti-NP and anti-RBD levels were reduced significantly after six months. Eleven patients who were anti-NP seropositive at time zero, had no detectable antibody at six months; of whom eight were found to have SARS-CoV-2 antigen specific T cell responses. Independent of antibody status at six months, patients with baseline positive SARS-CoV-2 serology were significantly less likely to have PCR confirmed infection over the following six months. Thus, patients receiving ICHD mount durable immune responses six months post SARS-CoV-2 infection, with fewer than 3% of patients showing no evidence of humoral or cellular immunity.

Informing the Risk of Kidney Transplantation Versus Remaining on the Waitlist in the Coronavirus Disease 2019 Era.

INTRODUCTION: There are limited data pertaining to comparative outcomes of remaining on dialysis versus kidney transplantation as the threat of coronavirus disease 2019 (COVID-19) remains. In this study we delineate the differential risks involved using serologic methods to help define exposure rates. METHODS: From a cohort of 1433 patients with end-stage kidney disease (ESKD), we analyzed COVID-19 infection rates and outcomes in 299 waitlist patients compared with 237 transplant recipients within their first year post-transplant. Patients were followed over a 68-day period from the time our transplant program closed due to COVID-19. RESULTS: The overall mortality rates in waitlist and transplant populations were equivalent (P = 0.69). However, COVID-19 infection was more commonly diagnosed in the waitlist patients (P = 0.001), who were more likely to be tested by reverse transcriptase polymerase chain reaction (P = 0.0004). Once infection was confirmed, mortality risk was higher in the transplant patients (P = 0.015). The seroprevalence in dialysis and transplant patients with undetected infection was 18.3% and 4.6%, respectively (P = 0.0001). After adjusting for potential screening bias, the relative risk of death after a diagnosis of COVID-19 remained higher in transplant recipients (hazard ratio = 3.36 [95% confidence interval = 1.19-9.50], P = 0.022). CONCLUSIONS: Although COVID-19 infection was more common in the waitlist patients, a higher COVID-19‒associated mortality rate was seen in the transplant recipients, resulting in comparable overall mortality rates.

High Prevalence of Asymptomatic COVID-19 Infection in Hemodialysis Patients Detected Using Serologic Screening.

BACKGROUND: Strategies to minimize the risk of transmission and acquisition of COVID-19 infection in patients with ESKD receiving in-center hemodialysis have been rapidly implemented across the globe. Despite these interventions, confirmed COVID-19 infection rates have been high in the United Kingdom. Prevalence of asymptomatic disease in an adult hemodialysis population has not been reported. Also, to our knowledge, the development of humoral response to SARS-CoV-2 has not been previously reported in this population. Although serologic testing does not provide information on the infectivity of patients, seroprevalence studies may enable investigation of exposure within dialysis units and hence, assessment of current screening strategies. METHODS: To investigate the seroprevalence of SARS-CoV-2 antibodies in a hemodialysis population, we used the Abbott IgG assay with the Architect system to test serum samples from 356 patients receiving in-center hemodialysis for SARS-CoV-2 antibodies. RESULTS: Of 356 patients, 121 had been symptomatic when screened before a dialysis session and received an RT-PCR test; 79 (22.2% of the total study population) tested positive for COVID-19. Serologic testing of all 356 patients found 129 (36.2%) who tested positive for SARS-CoV-2 antibodies. Only two patients with PCR-confirmed infection did not seroconvert. Of the 129 patients with SARS-CoV-2 antibodies, 52 (40.3%) had asymptomatic disease or undetected disease by PCR testing alone. CONCLUSIONS: We found a high seroprevalence of SARS-CoV-2 antibodies in patients receiving in-center hemodialysis. Serologic evidence of previous infection in asymptomatic or PCR-negative patients suggests that current diagnostic screening strategies may be limited in their ability to detect acute infection.

Bochdalek hernias associated with intrathoracic kidney: A case report and systematic review of outcomes including renal function.

BACKGROUND: An intrathoracic kidney is a very rare form of ectopic kidney. Though increasingly recognized in the literature, impact on renal function is less well described. We report the case of a 67-year-old South Asian gentleman who presented with intrathoracic kidney and chronic kidney disease. We carried out a systematic review of the available literature on intrathoracic kidney, in order to characterize the typical clinical features, and describe likely clinical course and possible renal and extra-renal complications associated with this form of ectopia. MATERIALS AND METHODS: A structured search using PubMed identified all relevant published case reports from 1988 to 2018, with search restricted to papers in English, and to adult cases only (> 18 years of age). 124 records were identified, and after screening for eligibility, 34 case reports were analyzed. RESULTS: Median age was 53.5 years, with no gender predominance. 68% (27/34) of cases were symptomatic. 29% (10/34) had a significant complication associated with their intrathoracic kidney, with 3 cases with either documented chronic or end-stage kidney disease. 26% (9/34) required surgical intervention. CONCLUSION: Though previously regarded as a benign entity, results from our systematic review, bearing in mind susceptibility to publication bias, suggests an appreciable risk of symptoms, complications, and in the minority a risk to kidney function. We recommend close biochemical and imaging surveillance of affected patients, with low threshold for intervention in those with renovascular stenosis, reflux, or hydronephrosis.

Successful management of post-transplant focal segmental glomerulosclerosis with therapeutic plasma exchange and rituximab.

BACKGROUND: Post-transplant focal segmental glomerulosclerosis (FSGS) is associated with renal allograft loss. Currently, optimal treatment remains controversial. METHODS: The aim of our study was to examine the efficacy and safety of therapeutic plasma exchange (TPE), and rituximab (RTX), in the management of post-transplant FSGS. The treatment protocol consisted of RTX and monthly cycles of 5 plasma exchanges for 6 months. We treated 10 transplant recipients with biopsy-proven post-transplant FSGS. Lastly, we compared the studied group to a historic control group of nine patients with post-transplant FSGS. RESULTS: 9 out of 10 patients achieved remission after the conclusion of treatment (4 complete and 5 partial), while 1 patient did not respond to treatment. During the follow-up period, there was one graft loss and one patient died while in remission from unrelated complications. There was a significant reduction in mean uPCR between diagnosis (517.4 ± 524.2 mg/mmol) and last follow-up (87 ± 121.6 mg/mmol) in the patients with sustained remission (p = 0.026). There was no significant decline in eGFR in the eight relapse-free responders at the end of follow-up. (54.4 ± 16.7 from 49.8 ± 20.4 ml/min) (p = 0.6) An increased response rate to the combined TPE and RTX treatment was demonstrated, when compared to a historic control group of nine patients with post-transplant FSGS, as only five out of nine patients achieved remission (two complete and three partial) in that group. CONCLUSIONS: In this study, treatment with TPE and RTX appears to be safe, well tolerated and effective in the management of patients with post-transplant FSGS.

ABO incompatible living renal transplantation with a steroid sparing protocol.

BACKGROUND: ABO incompatible (ABOi) live-donor renal transplantation is a successful and accepted form of treatment for patients with renal failure. Although there is significant controversy as to how antiblood group antibodies should be removed and their resynthesis prevented, subsequent immunosuppressive regimes have all involved steroids. We and other groups have successfully used steroid sparing regimes for conventional ABO compatible transplantation and this study describes the use of our steroid sparing protocol in ABOi transplantation. METHODS: We have transplanted 10 ABOi patients using 1 week of steroids (prednisolone 1 mg/kg for 4 days, 0.5 mg/kg for 3 days and then stopped), tacrolimus and mycophenolate mofetil. Steroids were reintroduced in the event of rejection. RESULTS: Patient- and allograft-survival 1 year posttransplantation is 100%. Three patients experienced antibody-mediated rejection within 2 weeks of transplantation, which was successfully reversed. There has been no late rejection. Allograft function was similar to our live-donor ABO compatible transplant patients receiving a similar steroid sparing regime (12-month mean creatinine 131+/-15 micromol/L vs. 138+/-48 micromol/L; mean CrCl 63.2+/-22 mL/min vs. 56.7+/-20 mL/min). CONCLUSIONS: This study shows that ABOi live-donor transplantation can be successfully accomplished using a steroid-sparing protocol.

Heparin-induced thrombocytopenia: an uncommon but serious complication of heparin use in renal replacement therapy.

Heparin-induced thrombocytopenia (HIT) is an uncommon but potentially life-threatening complication of heparin therapy. Hemodialysis and hemofiltration patients are regularly exposed to heparin, which is used for extracorporeal anticoagulation. Type II HIT (HIT-II) is the rarer immune-mediated form and is of huge clinical significance. The clinical manifestation of HIT-II is characteristically with venous and arterial thrombotic events. However, systemic and pulmonary reactions have been reported. Type II HIT is due to antibodies to the heparin-platelet factor 4 complex, which induce a cascade of events leading to thrombocytopenia and thrombosis. Nowadays, with increasing availability of functional and immunoassay tests for HIT-associated antibodies, HIT diagnosis can be confirmed more readily. Hence, it is important to rapidly recognize, diagnose, and manage this syndrome early in hemodialysis patients with thrombocytopenia to avoid serious consequences resulting in morbidity and mortality. We report a case of HIT-II manifesting atypically as a "pseudopulmonary embolus" in a hemodialysis patient and discuss the clinical management of HIT.