Foley catheter with noble metal alloy coating for preventing catheter-associated urinary tract infections: a large, multi-center clinical trial.

BACKGROUND: Catheter-associated urinary tract infections (CAUTI) are among the most frequent healthcare-associated infections in the world. They are associated with increased mortality, prolonged hospital stay and increased healthcare costs. The objective of this study was to evaluate the efficacy of the noble metal alloy (NMA) coated BIP Foley Catheter in preventing the incidence of symptomatic CAUTI in a large cohort of patients in India. METHODS: This multi-center, prospective study included 1000 adult patients admitted to six hospitals across India for urology, surgery and ICU requiring urethral catheterization and admission for ≥ 48 h. Patients were allocated to the NMA-coated BIP Foley Catheter group or a non-coated control catheter group, with a randomization ratio of 3:1. CAUTI surveillance was conducted at study entry, upon catheter removal, and 2 days after catheter removal. For statistical analysis, categorical data (e.g. gender) were compared using the chi-square or Fischer test, and numerical data were compared using the two-sample t-test. Associations were evaluated using logistic regression. RESULTS AND CONCLUSIONS: The incidence of symptomatic CAUTI was reduced by 69% in the BIP Foley Catheter group compared to the control group (6.5 vs 20.8 CAUTI/1000 catheter days), with an incidence rate ratio of 0.31 (95% confidence interval: 0.21-0.46; p < 0.001). A reduction in the cumulative CAUTI incidence was evident in the BIP Foley Catheter group within 3 days after catheterization; this reduction was maintained up to ~ 30 days, and the largest reductions were seen between 3 and 11 days. There were no serious adverse events related to either catheter, and the percentage of patients with ≥ 1 adverse event was significantly lower in the NMA-coated BIP Foley Catheter group than in the control group (21.6% vs. 48.4%; p = 0.001). In conclusion, the NMA-coated BIP Foley Catheter was effective in reducing CAUTI and was well tolerated, with a lower incidence of adverse events compared to the uncoated catheter. Trial registration This study was registered prospectively (28 September 2015) in the Clinical Trials Registry of India (trial number CTRI/2015/09/006220; http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=12631&EncHid=&userName=bactiguard ).

In vitro differentiation of neural cells from human adipose tissue derived stromal cells.

BACKGROUND: Stem cells, including neural stem cells (NSCs), are endowed with self-renewal capability and hence hold great opportunity for the institution of replacement/protective therapy. We propose a method for in vitro generation of stromal cells from human adipose tissue and their differentiation into neural cells. MATERIALS AND METHODS: Ten grams of donor adipose tissue was surgically resected from the abdominal wall of the human donor after the participants' informed consents. The resected adipose tissue was minced and incubated for 1 hour in the presence of an enzyme (collagenase-type I) at 370C followed by its centrifugation. After centrifugation, the supernatant and pellets were separated and cultured in a medium for proliferation at 370C with 5% CO2 for 9-10 days in separate tissue culture dishes for generation of mesenchymal stromal cells (MSC). At the end of the culture, MSC were harvested and analyzed. The harvested MSC were subjected for further culture for their differentiation into neural cells for 5-7 days using differentiation medium mainly comprising of neurobasal medium. At the end of the procedure, culture cells were isolated and studied for expression of transcriptional factor proteins: orthodenticle homolog-2 (OTX-2), beta-III-tubulin (ß3-Tubulin), glial-fibrillary acid protein (GFAP) and synaptophysin-ß2. RESULTS: In total, 50 neural cells-lines were generated. In vitro generated MSC differentiated neural cells' mean quantum was 5.4 ± 6.9 ml with the mean cell count being, 5.27 ± 2.65 × 103/µl. All of them showed the presence of OTX-2, ß3-Tubulin, GFAP, synaptophysin-ß2. CONCLUSION: Neural cells can be differentiated in vitro from MSC safely and effectively. In vitro generated neural cells represent a potential therapy for recovery from spinal cord injuries and neurodegenerative disease.

Four-Way Kidney Exchange Transplant With Desensitization Increases Access to Living-Donor Kidney Transplant: First Report From India.

OBJECTIVES: This study reports our experience of the first 4-way kidney exchange transplant combined with desensitization in India, which allows increased access to living-donor kidney transplant for sensitized patients. MATERIALS AND METHODS: Four-way kidney exchange transplant procedures were approved by the ethics committee of our institution and the Organ Transplantation Authorization Committee of state governments of India (as per the Transplantation of Human Organs Act of India). The protocols conformed to Declaration of Istanbul principles and the ethical guidelines of the 1975 Helsinki Declaration. Written informed consent was obtained from patients, donors, and their guardians. RESULTS: In April 2016, our transplant team completed simultaneous 4-way kidney exchange transplant procedures without any medical (rejection and infections) or surgical complications. Reasons for being included for kidney exchange transplant were ABO incom-patible (2 recipients) and sensitization (2 recipients). All 4 recipients had stable graft function with no proteinuria and donor-specific antibody at 11-month follow-up on standard triple immunosup-pression. Patient and graft survival rates were both 100%. CONCLUSIONS: To the best of our knowledge, this is the first single-center report of 4-way kidney exchange transplant combined with desensitization from India. This procedure has the potential to expand living-donor kidney transplant in disadvantaged groups (eg, sensitized patients). Recipients who are hard to match due to high panel reactive antibody and difficult to desensitize due to strong donor-specific antibodies can receive a transplant with a combination of kidney exchange and desensitization. Our study suggests that 4-way kidney exchange transplant can be performed in developing countries (India) similar to that shown in programs in developed countries with team work, kidney exchange registry, and counseling.

Six years' experience of tolerance induction in renal transplantation using stem cell therapy.

Tolerance induction (TI) has been attempted with chimerism/clonal deletion. We report results of TI protocol (TIP) using stem cell therapy (SCT) included adipose derived mesenchymal stem cells (AD-MSC) and hematopoietic stem cells (HSC) in 10 living-donor related renal transplantation (LDRT) patients under non-myeloablative conditioning with Bortezomib, Methylprednisone, rabbit-anti-thymoglobulin and Rituximab, without using conventional immunosuppression. Transplantation was performed following acceptable lymphocyte cross-match, flow cross-match, single antigen assay and negative mixed lymphocyte reaction (MLR). Monitoring included serum creatinine (SCr), donor specific antibodies (DSA) and MLR. Protocol biopsies were planned after 100days and yearly in willing patients. Rescue immunosuppression was planned for rejection/DSA/positive MLR. Over mean 6±0.37year follow-up patient survival was 80% and death-censored graft survival was 90%. Mean SCr was 1.44±0.41mg/dL. This is the first clinical report of sustained TI in LDRT for 6years using SCT.

Pure retroperitoneoscopic donor nephrectomy in duplication of inferior vena cava: A series of four cases.

AIM: Complex vascular anatomy poses a major challenge to the donor surgeon. Here, we have described the technical nuances in retroperitoneoscopic living donor nephrectomy for the left kidney in the situations of a rare vascular anomaly of duplication of inferior vena. MATERIALS AND METHODS: Between September 2005 and June 2016, 1460 retroperitoneoscopic living donor nephrectomy were carried out in single surgical unit of our institution. Out of these four donors were found to have duplication of inferior vena cava (IVC). We retrospectively analyzed the prospectively collected data of these donors and studied the operative details for managing the duplicated limb of the IVC. RESULTS: The mean age of the donors was 42.5 (range 30-54) years. Mean body mass index was 26.9 (range 25.2-28.6) kg/m2. Mean operative time (defined as between giving skin incision to the skin closure [O. T]), was 230 (range 185-310 min). Mean Warm ischemia time (defined from clamping of the renal artery to the starting of the cold HTK perfusion, [WIT]) was 136 s (range 105-178 s). In two cases, the renal vein could be controlled distal to the duplicated limb. In one case, the duplicated limb was clipped while in another a stapler was used to take a cuff of IVC. CONCLUSION: Retroperitoneoscopic donor nephrectomy can be performed safely in cases of duplication of IVC. Preoperative computerized tomography angiography with vascular reconstruction and surgical expertise is desirable in carrying out the procedure.

Seventy-seven kidney paired donation transplantations at a single transplant centre in India led to an increase in living donor kidney transplantations in 2015.

BACKGROUND: To ascertain the validity of kidney paired donations (KPDs) as an alternative strategy for increasing living donor kidney transplantations (LDKTs) in an LDKT-dominated transplant programme since directed kidney transplantation, ABO-incompatible or crossmatch-positive pairs are not feasible due to costs and infectious complications. METHODS: This was a prospective single-centre study of 77 KPD transplantations (25 two-way, 7 three-way and 1 six-way exchange) from 1 January 2015 to 1 January 2016 of 158 registered donor recipient pairs. During this period, a total of 380 kidney transplantations [71 deceased donor kidney transplantations (DDKTs), 309 LDKTs] were performed. The reasons for opting for KPD were ABO incompatibility (n = 45), sensitization (n = 26) and better matching (n = 6). RESULTS: KPD matching was facilitated in 62% (n = 98) of transplants. In all, 48.7% (n = 77) of the transplants were completed in 2015, whereas 13.3% (n = 21) of the matched patients were to undergo transplant surgery in early 2016 after getting legal permission. The waiting time for KPD was shorter compared with DDKT. The death-censored graft survival and patient survival were 98.7% (n = 76) and 93.5% (n = 72), respectively. In all, 14.2% (n = 11) of patients had acute rejection. Match rates among sensitized (n = 60) and O group patients (n = 62) were 58.3% (n = 35) and 41.9% (n = 26), respectively. Of these, 43.3% (n = 26) and 29% (n = 18) of transplants were completed and 15% (n = 9) and 12.9% (n = 8), respectively, are waiting for legal permission. CONCLUSIONS: LDKT increased by 25% in 1 year in our single-centre KPD programme. Our key to success was the formation of a KPD registry, awareness and active counselling programs and developing a dedicated team.

Repercussions of eosinophils in a renal allograft - Predictor of early graft loss!

We present 5-year experience of renal transplantation (RT) with tissue eosinophilia (TE) in renal allograft biopsy (RAB) and its repercussions on the outcome. In total, 1217 recipients underwent RT from 2011 to 2015, and they were evaluated for the presence of ≥4% TE. Group 1 consisted of RT with RAB showing TE, Group 2 consisted of RT with RAB with rejections without TE, and Group 3 consisted of RT without rejections. Group 1 had 27 recipients, Group 2 had 395, and Group 3 had 795 recipients. The outcome in terms of graft function, patient and graft survival were evaluated and compared between three groups. All recipients received standard triple immunosuppression. One-year patient and death-censored graft survival were 80.7% and 82.7% in Group 1, 87.2% and 95.1% in Group 2, and 92.6% and 99.6%, respectively in Group 3 and corresponding mean serum creatinine (SCr, mg/dL) was 1.60 ± 0.45 in Group 1, 1.63 ± 0.58 in Group 2, and 1.19 ± 0.39 Group three, respectively. Five-year patient and death-censored graft survival were 72.9 % and 71.1% for Group 2 and 87% and 98.2% for Group 3 with SCr of 1.63 ± 0.38 and 1.25 ± 0.4, respectively. Group 1 recipients did not appear at five years. At four years posttransplant, patient and death-censored graft survival were 71.7% and 59.5% in Group 1 with SCr of 1.55 ± 0.65 mg/dL. In conclusion, the presence of eosino-phils in a renal allograft is an impending sign of graft damage and eventual graft loss.

Stem cells: An emerging novel therapeutic for type-1 diabetes mellitus.

Stem cell based strategies are therapeutically potent for treating type-1 diabetes mellitus owing to their intrinsic regenerative capacity and immunomodulatory properties to arrest autoimmune ß-cell destruction, preserve residual ß-cell mass, facilitate endogenous regeneration, ameliorate innate/ alloimmune graft rejection, restore ß-cell-specific unresponsiveness in absence of chronic immunosuppression and to reverse hyperglycemia.

Past, present and future of kidney paired donation transplantation in India.

One third of healthy willing living kidney donors are rejected due to ABO blood group incompatibility and donor specific antibody. This increases pre-transplant dialysis duration leading to increased morbidity and mortality on the kidney transplantation waiting list. Over the last decade kidney paired donation is most rapidly increased source of living kidney donors. In a kidney transplantation program dominated by living donor kidney transplantation, kidney paired donation is a legal and valid alternative strategy to increase living donor kidney transplantation. This is more useful in countries with limited resources where ABO incompatible kidney transplantation or desensitization protocol is not feasible because of costs/infectious complications and deceased donor kidney transplantation is in initial stages. The matching allocation, ABO blood type imbalance, reciprocity, simultaneity, geography were the limitation for the expansion of kidney paired donation. Here we describe different successful ways to increase living donor kidney transplantation through kidney paired donation. Compatible pairs, domino chain, combination of kidney paired donation with desensitization or ABO incompatible transplantation, international kidney paired donation, non-simultaneous, extended, altruistic donor chain and list exchange are different ways to expand the donor pool. In absence of national kidney paired donation program, a dedicated kidney paired donation team will increase access to living donor kidney transplantation in individual centres with team work. Use of social networking sites to expand donor pool, HLA based national kidney paired donation program will increase quality and quantity of kidney paired donation transplantation. Transplant centres should remove the barriers to a broader implementation of multicentre, national kidney paired donation program to further optimize potential of kidney paired donation to increase transplantation of O group and sensitized patients. This review assists in the development of similar programs in other developing countries.

An unusual presentation of LCAT deficiency as nephrotic syndrome with normal serum HDL-C level.

Clinical and biochemical manifestations of lecithin-cholesterol acyltransferase (LCAT) deficiency include an abnormal lipid profile (characterized by hypercholesterolemia with markedly decreased high-density lipoprotein cholesterol [HDL-C] and hypertriglyceridemia), corneal opacities, hematologic abnormalities (normochromic anemia of varying intensity), splenomegaly, variable early coronary artery disease and nephropathy (initially proteinuria followed by progressive deterioration of renal function). We presented a patient with nephrotic syndrome, which renal biopsy revealed classic features of LCAT deficiency. To our knowledge, the present case is the first reported case of LCAT deficiency presenting with symptoms related to nephrotic syndrome in a patient with no obvious family history without any corneal deposits and normal HDL-C levels.

In-vitro generation of interleukin-10 secreting B-regulatory cells from donor adipose tissue derived mesenchymal stem cells and recipient peripheral blood mononuclear cells for potential cell therapy.

BACKGROUND: Interleukin-10 secreting B-cells are a major subset of B-regulatory cells (B-regs), commonly recognized as CD19+/38hi/24hi/IL10+. They carry out immunomodulation by release of specific cytokines and/or cell-to-cell contact. We have generated B-regs in-vitro from donor adipose tissue derived mesenchymal stem cells (AD-MSC) and renal allograft recipient (RAR) peripheral blood mononuclear cells (PBMC) for potential cell therapy. MATERIAL AND METHODS: Mononuclear cells separated by density gradient centrifugation from 50 ml anti-coagulated blood of 15-RAR and respective donors were analysed for baseline B-regs using appropriate antibodies. Equal amount (20 × 106 cells/ml) of stimulator (irradiated at 7.45 Gy/min for 10 min) and responder (non-irradiated) cells were co-cultured with in-vitro generated AD-MSC (1 × 106 cells/ml) in proliferation medium containing lipopolysaccharide from E. coli K12 strain at 37 °C with 5% CO2. Cells were harvested on day-7 and analyzed for viability, sterility, quantity, morphology and phenotyping. In-vitro generated B-reg levels were compared with baseline B-regs. RESULTS: In-vitro generated B-reg count increased to 16.75% from baseline count of 3.35%. CONCLUSION: B-regs can be successfully generated in-vitro from donor AD-MSC and RAR PBMC for potential cell therapy.

Impact of single centre kidney paired donation transplantation to increase donor pool in India: a cohort study.

In a living donor kidney transplantation (LDKT) dominated transplant programme, kidney paired donation (KPD) may be a cost-effective and valid alternative strategy to increase LDKT in countries with limited resources where deceased donation kidney transplantation (DDKT) is in the initial stages. Here, we report our experience of 300 single-centre KPD transplantations to increase LDKT in India. Between January 2000 and July 2016, 3616 LDKT and 561 DDKT were performed at our transplantation centre, 300 (8.3%) using KPD. The reasons for joining KPD among transplanted patients were ABO incompatibility (n = 222), positive cross-match (n = 59) and better matching (n = 19). A total of 124 two-way (n = 248), 14 three-way (n = 42), one four-way (n = 4) and one six-way exchange (n = 6) yielded 300 KPD transplants. Death-censored graft and patient survival were 96% (n = 288) and 83.3% (n = 250), respectively. The mean serum creatinine was 1.3 mg/dl at a follow-up of 3 ± 3 years. We credit the success of our KPD programme to maintaining a registry of incompatible pairs, counselling on KPD, a high-volume LDKT programme and teamwork. KPD is legal, cost effective and rapidly growing for facilitating LDKT with incompatible donors. This study provides large-scale evidence for the expansion of single-centre LDKT via KPD when national programmes do not exist.

International kidney paired donation transplantations to increase kidney transplant of O group and highly sensitized patient: First report from India.

AIM: To report the first international living related two way kidney paired donation (KPD) transplantation from India which occurred on 17th February 2015 after legal permission from authorization committee. METHODS: Donor recipient pairs were from Portugal and India who were highly sensitized and ABO incompatible with their spouse respectively. The two donor recipient pairs had negative lymphocyte cross-matching, flow cross-match and donor specific antibody in two way kidney exchange with the intended KPD donor. Local KPD options were fully explored for Indian patient prior to embarking on international KPD. RESULTS: Both pairs underwent simultaneous uneventful kidney transplant surgeries and creatinine was 1 mg/dL on tacrolimus based immunosuppression at 11 mo follow up. The uniqueness of these transplantations was that they are first international KPD transplantations in our center. CONCLUSION: International KPD will increases quality and quantity of living donor kidney transplantation. This could be an important step to solving the kidney shortage with additional benefit of reduced costs, improved quality and increased access for difficult to match incompatible pairs like O blood group patient with non-O donor and sensitized patient. To the best of our knowledge this is first international KPD transplantation from India.

Invasive fungal infections in renal transplant patients: a single center study.

BACKGROUND: Timely diagnosis of invasive fungal infections (IFI) in renal transplant (RT) patients on immunosuppression is often difficult, jeopardizing their life and graft. We reported IFI and their causative fungal agents in post-RT patients. MATERIALS AND METHODS: This was a retrospective 6-year clinical study carried out from 2010 to 2015 on 1900 RT patients. Clinical data included patient-donor demographics, time to onset of infection, risk factors and graft function in terms of serum creatinine (SCr). To identify IFI, we examined bronchoalveolar lavage (BAL), blood, tissue, and wound swab samples by conventional mycological methods. RESULTS: IFI were diagnosed in 30 (1.56%) patients on triple immunosuppression, mainly males (n = 25) with mean age of 36.57 ± 11.9 years at 13.12 ± 18.35 months post-RT. Aspergillus species was identified in 11 BAL, one tissue, and one wound specimen each, 30.76% of these were fatal and 15.38% caused graft loss; Candida albicans was in nine BAL, four blood, two wound swab, and one tissue specimens, 25% of these were fatal and 25% had graft loss and one mucor in BAL which was fatal. Seven patients were diabetic, 10 had superadded cytomegalovirus infection, and 15 were anti-rejected. CONCLUSION: IFI are associated with increased morbidity and mortality in RT patients. Triple immunosuppression, broad spectrum antibiotics for ≥ two weeks, diabetes and superadded infection are added risks for these patients. Prevention, early diagnosis, and appropriate management are necessary to improve their prognosis.

Stem cell therapy: An emerging modality in glomerular diseases.

The kidney has been considered a highly terminally differentiated organ with low proliferative potential and thus unlikely to undergo regeneration. Glomerular disease progresses to end-stage renal disease (ESRD), which requires dialysis or renal transplantation for better quality of life for patients with ESRD. Because of the shortage of implantable kidneys and complications such as immune rejection, septicemia and toxicity of immunosuppression, kidney transplantation remains a challenge. Therapeutic options available for glomerular disease include symptomatic treatment and strategies to delay progression. In an attempt to develop innovative treatments by promoting the limited capability of regeneration and repair after kidney injury and overcome the progressive pathological process that is uncontrolled with conventional treatment modalities, stem cell-based therapy has emerged as novel intervention due to its ability to inhibit inflammation and promote regeneration. Recent developments in cell therapy have demonstrated promising therapeutic outcomes in terms of restoration of renal structure and function. This review focuses on stem cell therapy approaches for the treatment of glomerular disease, including the various cell sources used and recent advances in preclinical and clinical studies.

Six end-stage renal disease patients benefited from first non-simultaneous single center 6-way kidney exchange transplantation in India.

AIM: To avoid desensitization protocols and ABO incompatible kidney transplantation (KT) due to high costs and increased risk of infections from intense immunosuppression. METHODS: We present institutional ethical review board - approved study of single center 6-way kidney exchange transplantation. The participants comprised ABO incompatibility (n = 1); positive cross-match and/or presence of donor specific antibody (n = 5). The average time required from registration in kidney paired donation (KPD) registry to find suitable donors was 45 d and time required to perform transplants after legal permission was 2 mo. RESULTS: Graft and patient survival were 100%, and 100%, respectively. One patient had biopsy-proven acute borderline T cell rejection (Banff update 2013, type 3). Mean serum creatinine was 0.8 mg/dL at 9 mo follow-up. The waiting time in KPD was short as compared to deceased donor KT. CONCLUSION: We report first non-simultaneous, single center, 6-way kidney exchange transplantation from India. Our experience will encourage other centers in India to undertake this practice.

Increasing access to kidney transplantation for sensitized recipient through three-way kidney paired donation with desensitization: The first Indian report.

The combination of kidney paired donation (KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation (LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT.

Pheohyphomycosis in Renal Transplant Recipient Presenting as a Rare Case of Submandibular Salivary Gland Swelling.

Renal transplant patients are at high risk of developing various infections causing morbidity and mortality. Invasive fungal infection has been recognized as a significant complication of organ transplantation. The major fungal infections in these patients are due to candida, aspergillus and mucormycosis. However, infection because of infrequently encountered fungi like hyaline molds, dematiaceous filamentous fungi and zygomycetes are increasing in immunocompromised hosts. Dematiaceous fungi are recognized pathogens in organ transplant recipients with skin and soft tissue infection. We report the case of a 37-year-old man, a renal transplant recipient who developed an asymptomatic dematiaceous fungal infection in submandibular salivary gland. He recovered after excision and antifungal therapy.