Nirav Shah

Two Hundred Living Donor Kidney Transplantations Under Alemtuzumab Induction and Tacrolimus Monotherapy: 3-Year Follow-Up

Alemtuzumab has been used in off‐label studies of solid organ transplantation. We extend our report of the first 200 consecutive living donor solitary kidney transplantations under alemtuzumab pretreatment with tacrolimus monotherapy and subsequent spaced weaning to 3 years of follow‐up. We focused especially on the causes of recipient death and graft loss, and the characteristics of rejection. The actuarial 1‐, 2‐ and 3‐year patient and graft survivals were 99.0% and 98.0%, 96.4% and 90.8% and 93.3% and 86.3%, respectively. The cumulative incidence of acute cellular rejection (ACR) at the following months was 2%≤6, 9.0%≤12, 16.5%≤18, 19.5%≤24, 23.5%≤30, 24.0%≤36 and 25%≤42. The mean serum creatinine (mg/dL) and glomerular filtration rate (mL/min/1.73 m2) at 1 and 3 years were 1.4 ± 0.6 and 58.7 ± 21.6 and 1.5 ± 0.7 and 54.9 ± 20.9, respectively. Fifty (25%) recipients had a total of 89 episodes of ACR. About 88.7% of ACR episodes were Banff 1, and of those, 82% were steroid‐sensitive. Nine (4.5%) recipients had antibody‐mediated rejection (AMR). About 76.5% were weaned but only 46% are currently on spaced dose (qod or less) tacrolimus monotherapy, and 94.4% remained steroid‐free from the time of transplantation. Infectious complications were uncommon. This experience suggests the 3‐year efficacy of this approach.

Kidney Transplantation in Elderly People: The Influence of Recipient Comorbidity and Living Kidney Donors

OBJECTIVES: To examine the extent to which donor and recipient characteristics were associated with transplant outcomes in elderly kidney transplant recipients.

Resistant Hypertension and Obstructive Sleep Apnea in the Setting of Kidney Disease

Objectives: To explore the relationship between obstructive sleep apnea (OSA) and resistant hypertension in chronic kidney disease (CKD) and end-stage renal disease (ESRD). Methods: We examined sleep parameters and blood pressure (BP) in 224 community-based, non-CKD participants from the Sleep-SCORE study: 88 nondialysis-dependent CKD and 95 ESRD participants. Unattended home polysomnography with standardized scoring protocols and automated BP monitors were used. Resistant hypertension was defined as a BP of at least 140/90 mmHg despite at least three antihypertensive drugs. Results: Mean SBP of the CKD and ESRD groups were significantly higher than that of the non-CKD group [148.2 (23.8), 144.5 (26.7) vs. 132.2 mmHg (26.7), respectively; P < 0.0001] despite the use of more antihypertensive medications. The CKD and ESRD groups had higher rates of resistant hypertension than the non-CKD group (41.4, 22.6 vs. 6.7%, respectively; P < 0.0001). The severity of sleep apnea was associated with a higher risk of resistant hypertension. Although resistant hypertension was associated with severe sleep apnea in participants with ESRD [odds ratio (OR) 7.1, 95% confidence interval (CI) 2.2–23.2), there was no significant association in the non-CKD (OR 3.5, 95% CI 0.8–15.4) or CKD groups (OR 1.2, 95% CI 0.4–3.7) after accounting for case-mix. Conclusion: The association between resistant hypertension and sleep apnea appeared robust in ESRD. OSA may contribute to resistant hypertension or both may be linked to a common underlying process such as volume excess. Future studies in patients with kidney disease should further characterize the resistant hypertension–OSA relationship and determine whether treatment of underlying mechanisms may improve outcomes.

Prevalence and correlates of fatigue in chronic kidney disease and end-stage renal disease: are sleep disorders a key to understanding fatigue?

Background: Fatigue is an important symptom to patients with advanced chronic kidney disease (CKD). The aim of this study is to examine the prevalence and severity of fatigue among non-dialysis-dependent CKD and end-stage renal disease (ESRD) patients, to examine the association of fatigue with subjective and objective sleep quality, and to identify other modifiable factors associated with fatigue. Methods: A cross-sectional survey of 87 non-dialysis-dependent CKD (eGFR ≤45 ml/min/1.73 m2) and 86 ESRD patients was done using the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) and 36-Item Short-Form (SF-36) vitality scale. Higher FACIT-F score denoted less fatigue. Objective sleep was assessed using in-home polysomnography. Predictors of fatigue were determined using a linear regression model. Results: The mean FACIT-F score among all participants was 34.5 ± 11.0. Mean scores were similar among CKD and ESRD groups (34.25 ± 11.28 vs. 34.73 ± 10.86; p = 0.73). On univariate analyses, patients with higher levels of fatigue were more likely to have cardiovascular disease, benzodiazepine use, depressive symptoms, and slightly lower hemoglobin and serum albumin levels. There was no significant association between severity of sleep apnea and level of fatigue (Apnea Hypopnea Index 20.1 ± 27.6 vs. 20.3 ± 22.0; p = 0.69). Presence of cardiovascular disease, low serum albumin, depressive symptoms, poor subjective sleep quality, excessive daytime sleepiness and restless legs syndrome were independently associated with greater fatigue in multivariable regression models. The FACIT-F score correlated closely with the SF-36 vitality score (r = 0.81, p < 0.0001). Conclusions: Patients with advanced CKD and ESRD experience profound fatigue. Depressive symptoms, restless legs syndrome, excessive daytime sleepiness, and low albumin levels may provide targets for interventions to improve fatigue in patients with advanced CKD.

Cancer risk with alemtuzumab following kidney transplantation.

Alemtuzumab has been employed for induction therapy in kidney transplantation with low rates of acute rejection and excellent graft and patient survival. Antibody induction therapy has been linked to increased vulnerability to cancer. Data regarding malignancy rates with alemtuzumab are limited. We studied 1350 kidney transplant recipients (between 2001 and 2009) at the University of Pittsburgh Starzl Transplant Institute, for post‐transplant de novo and recurrent malignancy, excluding non‐melanoma skin cancer, among patients receiving alemtuzumab, thymoglobulin, and no induction therapies. Of the 1350 patients, 1002 (74.2%) received alemtuzumab, 205 (15.2%) received thymoglobulin, and 122 (9%) received no induction therapy. After excluding cancers occurring within 60 d post‐transplantation, 43 (3.25%) malignancies were observed during a median follow‐up time of 4.0 yr. The incidence of malignancy was 5.4% (1.09 per 100 patient‐years [PY]) with thymoglobulin, 2.8% (0.74 per 100 PY) with alemtuzumab, and 3.3% (0.66 per 100 PY) with no induction (across all groups; p = 0.2342, thymoglobulin vs. alemtuzumab; p = 0.008). Thus, with the exception of non‐melanoma skin cancer which we did not evaluate, alemtuzumab induction was not associated with increased cancer incidence post‐kidney transplantation when compared to no induction therapy and was associated with lower cancer incidence when compared to thymoglobulin.

Nocturia and Aging: Diagnosis and Treatment

Nocturia is a frequently encountered problem in clinical practice and a reason for nephrology consultation. Many studies have clearly shown the negative effect of nocturia on several aspects of health-related quality of life and morbidity. Age-associated physiological, structural, hormonal, and histological changes play an important role in the increasing incidence of nocturia in elderly individuals. Besides urologic conditions, nocturia may also be the initial presenting symptom in chronic kidney disease, as well as other systemic diseases. Therefore, it is essential to understand the complex pathophysiology among these factors to establish a precise diagnosis and appropriate management strategies. This review will provide an overview of the effect of aging on the kidneys and urinary system, the pathophysiology, clinical assessment, and treatment strategies of nocturia, and its effect on health-related quality of life.

Cold heparinized lactated Ringers with procaine (HeLP) preservation fluid in 266 living donor kidney transplantations.

Since the 1960s simple inexpensive cold lactated Ringers with additives has been used for short-term cold preservation of kidneys from living donors. We performed 266 living donor kidney transplantations from January 22, 2003 to October 30, 2006. Donor allografts were recovered laparoscopically and flushed with cold heparin, lactated Ringers and procaine (HeLP) solution. Warm and cold ischemic times were typically <45 min and <90 min, respectively. The mean follow up was 21.6±12.2 months. There was no delayed graft function. Actuarial 1-year patient and graft survival were 98.6% and 98.1%, respectively. The creatinine at 1 year was 1.46±0.51 mg/dL. The cumulative incidences of acute cellular rejection at 6, 12, 18, and 24 months were 3.0%, 7.1%, 10.2%, and 11.7%. There were no identifiable side effects attributed to the HeLP solution. This study documents the effectiveness of cold HeLP as a flushing and short-term preservation fluid for living donor kidney transplantation with excellent results and significant cost benefit because of its low cost.

Cytomegalovirus infection in high-risk kidney transplant recipients receiving thymoglobulin induction-a single-center experience.

The burden of cytomegalovirus infection in CMV high‐risk (donor positive to recipient negative) kidney transplant recipients getting thymoglobulin induction and six months of valganciclovir is not well characterized. Additionally, the role of post‐prophylaxis surveillance remains unclear.

Which of the K/DOQI guidelines for bone disease in dialysis patients should be changed?

The K-DOQI guidelines for bone metabolism in chronic kidney disease recommend measuring 25(OH) vitamin D levels and correcting deficiencies in stages 3 and 4 but not in ESRD. Most nephrologists are not concerned with 25(OH) vitamin D deficiency, despite evidence in hemodialysis patients that deficient vitamin D status [as measured by 25(OH) vitamin D levels] plays a role in bone disease. PD patients are often deficient in 25(OH) vitamin D in part because of peritoneal effluent losses, and correction may decrease muscle and bone complaints. Data from other populations are indicative of the importance of vitamin D in cancer surveillance and immune functioning. Randomized controlled trials of correction of 25(OH) vitamin D deficiency in both hemodialysis and peritoneal dialysis patients are urgently needed. vitamin D).

Short-term adverse effects of early subclinical allograft inflammation in kidney transplant recipients with a rapid steroid withdrawal protocol

The impact of subclinical inflammation (SCI) noted on early kidney allograft biopsies remains unclear. This study evaluated the outcome of SCI noted on 3‐month biopsy. A total of 273/363 (75%) kidney transplant recipients with a functioning kidney underwent allograft biopsies 3‐months posttransplant. Among those with stable allograft function at 3 months, 200 biopsies that did not meet the Banff criteria for acute rejection were identified. These were Group I: No Inflammation (NI, n = 71) and Group II: Subclinical Inflammation (SCI, n = 129). We evaluated differences in kidney function at 24‐months and allograft histology score at 12‐month biopsy. SCI patients had a higher serum creatinine (1.6 ± 0.7 vs 1.38 ± 0.45; P = .02) at 24‐months posttransplant, and at last follow‐up at a mean of 42.5 months (1.69 ± 0.9 vs 1.46 ± 0.5 mg/dL; P = .027). The allograft chronicity score (ci + ct + cg + cv) at 12‐months posttransplant was higher in the SCI group (2.4 ± 1.35 vs 1.9 ± 1.2; P = .02). The incidence of subsequent rejections within the first year in SCI and NI groups was 24% vs 10%, respectively (P = .015). De novo donor‐specific antibody within 12 months was more prevalent in the SCI group (12/129 vs 1/71, P = .03). SCI is likely not a benign finding and may have long‐term implications for kidney allograft function.