HLA Desensitization Based on Results of the Luminex Technique in Kidney Transplant - A Single-center Experience.

BACKGROUND: There is little experience of human leucocyte antigen (HLA) desensitization in India based on the Luminex single-antigen bead (SAB) testing. We retrospectively analyzed our patients, who underwent HLA desensitization based on Luminex SAB results. METHOD: Between 2014 and 2018, patients with complement-dependent cytotoxicity cross-match (CDC-XM) negativity but flow cytometry crossmatch (FC-XM) positivity were further analyzed with Luminex SAB for donor-specific antibodies (DSAs). A total of 12 patients who had DSA mean fluorescent intensity (MFI) of >1000 and <10,000 were included in the study. Our protocol for desensitization consisted of plasmapheresis (PP) followed by low dose intravenous immunoglobulin (IV IG) 100 mg/kg and induction with antithymocyte globulin (ATG). Patients were taken for transplant when either MFI was <1000 and/or FC-XM was negative. RESULTS: All 12 patients were first transplant and 10 had a history of some sensitizing event; pregnancy in 4, blood transfusions in 4, and both in 2 patients. FC-XM was positive for T-cell in 4, B-cell in 6, and both in 2 patients. On evaluation by Luminex SAB, 6 patients had MFI from 1000 to 2000, and 6 had MFI of >2000. All underwent desensitization successfully. Two patients had an increase in posttransplant DSA titers requiring posttransplant PP. The mean follow-up was 26.6 ± 13.9 months. On follow-up, only one patient developed acute T cell-mediated rejection 1 year after transplant, which responded to pulse steroids. There was no graft or patient loss until the last follow-up. CONCLUSION: This study shows that HLA desensitization is feasible and successful in the Indian setting if patients are properly selected.

The Adverse Effect of COVID Pandemic on the Care of Patients With Kidney Diseases in India.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has affected the care of patients with noncommunicable diseases, including those suffering from kidney-related ailments. Many parts of the world, including India, adopted lockdown to curb community transmission of disease. The lockdown affected transportation, access to health care facilities, and availability of medicines and consumables as well as outpatient and inpatient services. We aimed to analyze the effect of lockdown imposed due to the COVID-19 pandemic on the care of patients with kidney diseases in India. METHODS: We surveyed 19 major hospitals (8 in the public and 11 in the private sector) to determine the effect of lockdown on the care of patients with kidney disease, including those on dialysis after the first 3 weeks of lockdown. RESULTS: The total number of dialysis patients in these centers came down from 2517 to 2404. Approximately 710 (28.2%) patients missed 1 or more dialysis sessions, 69 (2.74%) required emergency dialysis sessions, 104 (4.13%) stopped reporting for dialysis, and 9 (0.36%) were confirmed to have died. Outpatient attendance in the surveyed hospital came down by 92.3%, and inpatient service reduced by 61%. Tele-consultation was started but was accessed by only a small number of patients. CONCLUSION: Lack of preparedness before lockdown resulted in an interruption in health care services and posed an immediate adverse effect on the outcome of dialysis patients and patients with kidney disease in India. The long-term impact on the health of patients with less severe forms of kidney disease remains unknown.

Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome.

Hypertension is common in hemolytic uremic syndrome (HUS) and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV) enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency.

Remission of post-transplant focal segmental glomerulosclerosis with angiotensin receptor blockers.

Recurrence of focal segmental glomerulosclerosis (FSGS) is common after kidney transplantation. Plasmapheresis (PP) is considered to be the most effective treatment; however, results are variable and relapse is common after stopping plasmapheresis. Here, we report an unusual case of recurrent FSGS, who achieved complete remission with angiotensin receptor blocker therapy.

Eculizumab for atypical hemolytic-uremic syndrome in India: First report from India and the challenges faced.

Much progress has been made in understanding the pathophysiology and treatment of atypical hemolytic uremic syndrome (aHUS). Plasma therapy is the mainstay of treatment for aHUS. The availability of the first effective anti-complement therapeutic agent, eculizumab, has dramatically changed the outlook of this disease. However, its use in clinical practice raises important questions, such as who should receive the drug, when to start such therapy, and is it safe to stop treatment once the disease is controlled. We describe here for the 1st time in India, use of eculizumab in a 12-year-old boy with aHUS. We also describe in this report challenges faced in procuring the drug, and an ideal, evidence-based method of treating aHUS in children.

ABO-incompatible renal transplantation in developing world - crossing the immunological (and mental) barrier.

ABO incompatibility has been considered as an important immunological barrier for renal transplantation. With the advent of effective preconditioning protocols, it is now possible to do renal transplants across ABO barrier. We hereby present a single center retrospective analysis of all consecutive ABOi renal transplants performed from November 2011 to August 2014. Preconditioning protocol consisted of rituximab, plasmapheresis and intravenous immunoglobulin (IVIG) and maintenance immunosuppression consisted of tacrolimus, mycophenolate sodium, and prednisolone. The outcome of these ABOi transplants was compared with all other consecutive ABO-compatible (ABOc) renal transplants performed during same time. Twenty ABOi renal transplants were performed during the study period. Anti-blood group antibody titer varied from 1:2 to 1:512. Patient and graft survival was comparable between ABOi and ABOc groups. Biopsy proven acute rejection rate was 15% in ABOi group, which was similar to ABOc group (16.29%). There were no antibody-mediated rejections in ABOi group. The infection rate was also comparable. We conclude that the short-term outcome of ABOi and ABOc transplants is comparable. ABOi transplants should be promoted in developing countries to expand the donor pool.

Paired kidney exchange transplantation: Maximizing the donor pool.

In the last decade, paired kidney exchange (PKE) transplantation has gained popularity worldwide as a viable alternative for end stage renal disease (ESRD) patients who have incompatible or sensitized donors. This study presents our experience with PKE transplantation and compares outcome between PKE and non-PKE renal transplant recipients. Between February 2010 and November 2013, 742 transplants were performed, of which 26 (3.5%) were PKE transplantations. All were two-way exchanges. PKE recipients were significantly older than non-PKE (46.73 ± 9.71 vs. 40.08 ± 13.36 years; P = 0.012) while donor ages were comparable. PKE patients had significantly higher number of HLA mismatches (5.03 ± 1.14 vs. 3.49 ± 1.57; P < 0.0001). After a median follow-up of 20 months (range: 3-47 months), there was no significant difference in patient survival (PKE 96.16% vs. non-PKE 96.65%; P = 0.596) and death censored graft survival (PKE 96.16% vs. non-PKE 96.37%; P = 1). Mean serum creatinine at 1 month and at last follow-up was lower in PKE versus non-PKE group (0.98 ± 0.33 vs. 1.3 ± 0.61 mg/dl; P = 0.008 and 0.96 ± 0.30 vs. 1.27 ± 0.57 mg/dl, P = 0.006, respectively). Biopsy proven acute rejection rate was 11.5% in PKE group and 16.89% in non-PKE patients (P = 0.6). To conclude, paired kidney donation is an excellent way of increasing the donor pool and needs to be promoted to overcome the shortage of suitable kidney in our country.

Early corticosteroid withdrawal regimen in a living donor kidney transplantation program.

Steroids have been the essential component of transplant immunosuppression. Recently, with availability of better immunosuppressive agents, many centers have started steroid free transplant with good success rates. We analyzed the outcomes of early corticosteroid withdrawal (CSW) protocol in our living donor kidney transplant programme. We included 73 patients on CSW protocol on basiliximab + tacrolimus and mycophenolate mofetil and compared them with 67 recipients on similar regimen with corticosteroids (CSs). CSW group received prednisolone 40 mg on day 1, which was stopped on day 5. Outcomes were evaluated in terms of acute rejection (AR), infections, new onset diabetes after transplant (NODAT), renal function and graft or patient loss. In CSW group, 15/73 (20.5%) patients developed AR, when compared to 5/67 (7.5%) in CS group, (P = 0.02). Biopsy proven acute rejection was seen in 12/72 (16.6%) in CSW group and 5/67 (7.5%) in CS (P = 0.1). One patient in CSW group developed antibody mediated rejection. NODAT was similar (9% in CS vs. 3.7% in CSW, P = 0.09), but infections were higher in CSW group (20.5% vs. 7.5%, P = 0.02). Mean serum creatinine was similar at 6 months (1.24 ± 0.6 in CS and 1.25 ± 0.3 in CSW, P = 0.9). Graft survival was 100% and 97% (P = 0.1) and patient survival was 98.6% and 98.5% (P = 0.9) in CSW and CS groups. Early corticosteroid withdrawal with basiliximab induction was associated with increased risk of AR but did not have any effect on short term graft and pateint survival.

Comparison of azathioprine with mycophenolate mofetil in a living donor kidney transplant programme.

There are conflicting data regarding the comparative efficacy of mycophenolate mofetil (MMF) versus azathioprine (AZA) as maintenance immunosuppressive agent in kidney transplantation. The data are even less in combination with tacrolimus (TAC) in living donor kidney transplantation. A total of 205 living donor kidney transplants, on TAC-based triple drug immunosuppression were included in the study. A total of 113 patients received AZA and rest 92 were on MMF based protocol. TAC levels were monitored and graft biopsy was done whenever rejection was suspected. The outcomes were evaluated in terms acute rejection (AR) episodes at 1 year, infections, renal function, graft loss, and death between two groups. The study group comprised 163 males (79.5%) and 42 (20.5%) females. The mean age of patients was 42.4±11.8 years in the AZA group and 39.4 ±13.4 in the MMF group (P=0.09). The mean duration of follow-up was 491.7±240.7 and 478.8±334.4 days respectively in the AZA and MMF groups (P=0.75). Thirty-seven of 92 (40.2%) patients in the MMF group and 70/113 (61.9%) patients in the AZA group received IL-2 RAb induction (P=0.002). 32 patients (15.6 %) developed AR within a year. The incidence of AR was similar in patients who received MMF (12/92, 13%) and those who received AZA (20/113, 17.5%), (P=0.36). There was no difference in the incidence of AR in the subgroup of patients who received IL-2 RAb compared to those who did not receive induction in the two groups (5/37 vs. 7/55 in the MMF group and 10/70 vs. 10/43 in the AZA group, P=0.72). The incidence of infections was similar in the two groups (19/92, 20.6% vs. 25/113, 22.1%, P=0.79). Three patients developed CMV disease, of which two were in the MMF group. Graft loss occurred in 7/205 (3.4%) and death in 8/205 (3.9%) patients. Six of eight patients who died had functioning grafts. The rate of graft loss (3/92 vs. 4/113, P=0.97) and death (5/92 vs. 3/113, P=0.27) was similar in two groups. The overall patient survival was 94.5% and death censored graft survival was 97.4%. Cost comparison suggests AZA to be 6-10 times cheaper than MMF. This study suggests that, in tacrolimus-based immunosuppression, azathioprine may be as good as MMF as maintenance immunosuppressive drug in living donor kidney transplantation. It is also a more cost-effective immunosuppression.

Kidney transplantation in a patient with HIV disease.

Human immunodeficiency virus (HIV) disease was considered an absolute contraindication to kidney transplantation until recently. The main reason was the concern regarding the side effects of immunosuppressive drugs in already immunocompromised patients. Kidney transplantation is considered to be the best form of renal replacement therapy in most patients with kidney failure. Nowadays, many world medical centers are successfully doing kidney transplantation in HIV patients with kidney failure. However, HIV disease is still considered a contraindication to kidney transplantation in most Indian centers. Here, we report a case of a patient with HIV infection and ESRD, who underwent successful kidney transplantation in our center.

Chronic hepatitis C virus infection in renal transplant: treatment and outcome.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a common cause of liver disease in post-renal transplant period and causes poor patient and graft survival. We analyzed the effects of antiviral therapy using ribavirin monotherapy or ribavirin in combination with interferon (IFN)-alpha in our kidney transplant recipients with chronic hepatitis C. METHODS: Total of 14 patients received antiviral therapy, all of whom had stable graft function, raised aminotransferases and positive HCV viremia at the start of treatment. Eight patients received ribavirin alone for a period of six months to two yr, in doses of 400-800 mg daily. Five patients received IFN-alpha therapy for a period of two months to 1.5 yr, in doses of 1.5 million units daily or three million units thrice weekly with ribavirin. One patient received pegylated IFN 50 microg once weekly in combination with ribavirin. The response was seen in terms of biochemical and virological improvement at the end of study period. RESULTS: In patients treated with ribavirin alone (n = 8), mean alanine aminotransferase (ALT) levels before and after treatment were significantly different (198.4 +/- 147.6 and 104.8 +/- 66.5 IU/L respectively; p < 0.05). ALT levels normalized completely in three patients at the end of treatment, improved in three patients and deteriorated in two. Only in one of eight patients on ribavirin alone, HCV-RNA became negative after six months of treatment while in the rest (n = 7) HCV-RNA continued to be positive. In subjects on IFN plus ribavirin (n = 6), the mean ALT levels decreased significantly (from 280.2 +/- 114.9 IU/L at baseline to 71 +/- 49 IU/L at end of therapy; p < 0.05). Two patients had sustained remission (33.3%) on IFN plus ribavirin (persistently negative HCV-RNA), two patients relapsed after initial remission and in two patients treatment was stopped after two months because of graft dysfunction. Totally four patients developed graft dysfunction at some time during the course of IFN therapy (66.6%), but it was discontinued in only two (33.3%). All patients regained normal creatinine levels after discontinuation of IFN, although one patient developed chronic allograft nephropathy as shown by kidney biopsy. Four patients in IFN group developed leucopenia. Two patients developed severe anemia one of whom required blood transfusion and one developed severe flu-like syndrome requiring stoppage of therapy. CONCLUSION: Ribavirin monotherapy in renal transplant recipients with chronic hepatitis C infection results in good biochemical response but is not associated with virological clearance. IFN in combination with ribavirin is effective in two-thirds of patients after a minimum therapy of six months, but it is poorly tolerated, results in graft dysfunction in significant number of patients, and relapse can occur after stopping treatment.