The natural history of renal functional decline in patients undergoing surveillance in the DISSRM registry

ObjectiveTo describe the natural history of renal function in patients on active surveillance (AS) for small renal masses (SRM) in the Delayed Intervention and Surveillance for Small Renal Masses Registry.MethodsDelayed Intervention and Surveillance for Small Renal Masses is a prospective, multi-institutional registry of patients with SRM (≤4 cm) who choose intervention or AS. Of these, 64 patients on AS had longitudinal serum creatinine (sCr) values and underwent analysis of estimated glomerular filtration rate (eGFR). eGFR was calculated using the Modification of Diet in Renal Disease formula. The Kidney Disease Outcomes Quality Initiative chronic kidney disease (CKD) classification was used to categorize patients’ eGFR values.ResultsMedian age was 74 (range: 34–88) years at onset of AS. Overall, 9% (6/64) of patients had CKD at baseline. Median initial tumor size was 2.1 cm (range: 0.8–4.0). Median Charlson comorbidity index score was 4 (range: 0–8). Median baseline sCr was 1.0 mg/dl (range: 0.4–2.1) and median baseline eGFR was 70.25 (range: 24.07–165.52). After a median follow-up of 17 (range: 2–46) months, 64% of patients experienced a decrease in eGFR, with average yearly decrease in eGFR of 1.82 ml/min/1.73 m² (P = 0.092) and average yearly increase in sCr of 0.046 (P = 0.012). A total of 15 (24%) patients experienced an upstaging in classification of CKD.DiscussionNearly two-thirds of patients on AS experienced a decrease in eGFR and nearly one-fourth had upstaging of CKD classification. The annual eGFR decline experienced by patients on AS minimally exceeded the annual decline of 1.49±0.3 ml/min/1.73 m² that an individual who was 70 to 79 years of age can expect from aging alone. Further follow-up is necessary to assess this in a more definitive manner, but this trend should be considered when evaluating AS as an alternative to interventional therapies for SRM.     

The feasibility,time savings and economic impact of a designated time appointment system at a busy HIV care clinic in Kenya: a randomized controlled trial

Introduction

As efforts are made to reach universal access to ART in Kenya, the problem of congestion at HIV care clinics is likely to worsen. We evaluated the feasibility and the economic benefits of a designated time appointment system as a solution to decongest HIV care clinics.

Methods

This was an explanatory two-arm open-label randomized controlled trial that enrolled 354 consenting participants during their normal clinic days and followed-up at subsequent clinic appointments for up to nine months. Intervention arm participants were given specific dates and times to arrive at the clinic for their next appointment while those in the control arm were only given the date and had the discretion to decide on the time to arrive as is the standard practice. At follow-up visits, we recorded arrival and departure times and asked the monetary value of work participants engaged in before and after clinic. We conducted multiple imputation to replace missing data in our primary outcome variables to allow for intention-to-treat analysis; and analyzed the data using Mann–Whitney U test.

Results

Overall, 72.1% of the intervention participants arrived on time, 13.3% arrived ahead of time and 14.6% arrived past scheduled time. Intervention arm participants spent a median of 65 [interquartile range (IQR), 52–87] minutes at the clinic compared to 197 (IQR, 173–225) minutes for control participants (p<0.01). Furthermore, intervention arm participants were more productively engaged on their clinic days valuing their cumulative work at a median of USD 10.5 (IQR, 60.0–16.8) compared to participants enrolled in the control arm who valued their work at USD 8.3 (IQR, 5.5–12.9; p=0.02).

Conclusions

A designated time appointment system is feasible and provides substantial time savings associated with greater economic productivity for HIV patients attending a busy HIV care clinic.     

Unintended consequences of changes to lung allocation policy

Organ allocation for transplantation aims to balance the principles of justice and medical utility to optimally utilize a scarce resource. To address practical considerations, the United States is divided into 58 donor service areas (DSA), each constituting the first unit of allocation. In November 2017, in response to a lawsuit in New York, an emergency action change to lung allocation policy replaced the DSA level of allocation for donor lungs with a 250 nautical mile circle around the donor hospital. Similar policy changes are being implemented for other organs including heart and liver. Findings from a recent US Department of Health and Human Services report, supplemented with data from our institution, suggest that the emergency policy has not resulted in a change in the type of patients undergoing lung transplantation (LT) or early postoperative outcomes. However, there has been a significant decline in local LT, where donor and recipient are in the same DSA. With procurement teams having to travel greater distances, organ ischemic time has increased and median organ cost has more than doubled. We propose potential solutions for consideration at this critical juncture in the field of transplantation. Policymakers should choose equitable and sustainable access for this lifesaving discipline.     

Expanding the donor pool to increase renal transplantation.

INTRODUCTION: The goal of the Eurotransplant renal allocation scheme is to provide every patient on the waiting list with a reasonably balanced opportunity for a donor offer. New initiatives were taken in order to maximize donor usage while maintaining a successful transplant outcome. METHODS: Two Eurotransplant projects were launched in order to accommodate changes in donor and recipient profiles. A re-addressing of the non-heart-beating donor pool was undertaken and an allocation scheme in which organs from donors aged >65 are allocated to recipients aged >65 [the Eurotransplant Senior Programme (ESP)] was introduced. RESULTS: Especially in The Netherlands, an enormous increase in the number of non-heart-beating donor kidneys has been observed, however with a pace-keeping reduction in heart-beating donors. The organization-wide implementation of the ESP has been successful. The 3 year graft survival rates for these age-matched transplants were as good as the human leukocyte antigen (HLA)-matched transplants (64 vs 67%) (P = 0.4). CONCLUSION: Within the framework of sound research, the utmost flexibility and creativity is needed to keep or even increase the number of renal transplants when faced with a quantitatively stagnating but qualitatively deteriorating donor pool. Both the non-heart-beating donor protocol and the ESP have proven to be quite successful in achieving this goal without compromising the outcome for the individual end-stage renal disease patient.     

The impact of national guidelines on the waiting list for colonoscopy: a quantitative clinical audit

Objective To assess the compliance of the surveillance colonoscopy waiting list with ACPGBI/BSG guidelines for colonoscopy follow‐up and to measure the impact of adjusting referrals to be inline with the guidelines. Design and Setting This is a quantitative five‐stage clinical audit cycle involving a large patient cohort from the Kent and Medway Cancer Network, which includes seven hospitals across four NHS Hospital Trusts and an estimated population of 1.8 million. Participants 3020 patients were waiting for a surveillance colonoscopy. Their notes were reviewed and the indications for colonoscopy were compared with the ACPGBI/BSG 2002 guidelines. Interventions Those patients whose referral to the surveillance colonoscopy waiting list was not found to be compliant were adjusted to be inline with the guidelines. Main outcome measures The impact of adjusting the surveillance colonoscopy waiting list on the diagnostic colonoscopy service was assessed by measuring the average waiting times for a colonoscopy before and after the intervention. Results Around 22% (n = 664) of surveillance colonoscopy referrals were inline with the guidelines, 51% (n = 1540) could be cancelled from the list and 27% (n = 816) could be given a new date. Implementing these recommendations reduced the average wait for a diagnostic colonoscopy from 76.8 to 56.0 days (P = 0.0022). Conclusion Following guidelines for surveillance colonoscopy can reduce waiting times for diagnostic colonoscopy. This allows a faster patient journey for diagnostic colonoscopy and a uniform plan for duration and frequency of surveillance colonoscopy. However, this action promoted serious debate on the social, moral and ethical issues.     

The impact of the lung allocation scoring system at the single national Veterans Affairs Hospital lung transplantation program

Objective: The lung allocation score (LAS) has changed the distribution of donor lungs for transplantation. This study was undertaken to evaluate the impact of the LAS on a unique patient population undergoing lung transplantation (LTX) at the single national Veterans Affairs (VA) LT center. Methods: One hundred and ten consecutive VA patients underwent LTX between 1994 and 2007. Patients transplanted using the LAS (LAS, n = 26) were compared to patients transplanted prior to introduction of the LAS (pre-LAS, n = 84). Results: Waiting time decreased from 353.8 ± 254.7 (pre-LAS) to 238.0 ± 306.6 (LAS) days (p < 0.01). Recipient diagnoses have changed with an increase in idiopathic pulmonary fibrosis [11% (9/84) pre-LAS vs 46% (12/26) LAS, p < 0.01] and a decrease in emphysema [57% (48/84) pre-LAS vs 35% (9/26) LAS, p < 0.01]. Mean LAS calculation was 33.1 ± 2.9 for pre-LAS versus 41.9 ± 9.8 for the LAS (p < 0.01). Postoperative complications did not differ between the groups. Length of hospital stay decreased from 44.3 ± 42.9 (pre-LAS) to 18.1 ± 12.3 (LAS) days (p < 0.01). Hospital mortality and 1-year survival did not differ between the pre-LAS and LAS groups (7% vs 8%; p = 0.72 and 92% [95% confidence interval (CI) 86–98] vs 92% [CI 82–100]; p = 0.23, respectively). Conclusions: The LAS appears to be achieving its objectives by reducing waitlist time and altering the distribution of lung disease being transplanted on the basis of medical necessity in the U.S. VA population. In addition, the LAS does not appear to have adversely affected short-term post-transplant outcomes in our recipient cohort.     

Evaluation of the Eurotransplant Senior Program. The Results of the First Year

On 4 January 1999, the Eurotransplant Senior Program (ESP) was implemented within the Eurotransplant kidney allocation scheme. PATIENTS AND METHODS: Kidneys obtained from donors aged over 65 years of age (65+) were allocated to a selected group of nonimmunized 65+ patients undergoing their first transplant. All transplants were performed locally to minimize cold-ischemic time. All transplants performed with kidneys from elderly donors that were allocated via ESP (ESP group) were compared to transplants performed with similar kidneys allocated via the standard renal allocation system (control group). Initial kidney function and 1-year graft outcome were assessed. RESULTS: In 1999, 227 ESP and 102 control transplants were performed. The duration of cold-ischemic time was 12 and 19 h for the ESP and control groups, respectively. No rejection episodes occurred in 60% and 67% of the ESP patients and controls, respectively, while a direct kidney function was observed in 59% of ESP and 49% of control patients. The 1-year graft survival rates, censoring for graft losses due to deaths in patients with functioning grafts, were 86% and 79%, respectively. CONCLUSION: An old-for-old renal allocation algorithm can be successful provided that risk factors, such as cold-ischemic time, are reduced.     

The growth rate of large renal masses opposes active surveillance

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To retrospectively determine the growth rate of renal masses with a diameter of ≥4 cm at the time of surgery, as the average growth rate of untreated small (<4 cm) renal masses is assumed to be 0.1–0.7 cm/year, but little is known about the progression of large masses.

PATIENTS AND METHODS

Of 256 patients who had their renal tumour surgically removed between January and December 2008, we identified nine (five men and four women; median age 65.2 years, range 29.2–74.2) with solitary large renal masses (>4 cm) who had abdominal imaging with identification of renal masses >6 months before admission. In none of the patients had the initial imaging led to admission, either by accident or because the masses were overlooked. The tumour growth rate was calculated based on images taken ≥6 months before admission and actual imaging, as well as histological results.

RESULTS

All patients had surgical resection of their renal masses in 2008. The median (range) follow‐up from initial diagnosis to surgery was 14.6 (6.5–58.4) months. The median observed tumour growth rate was 6.41 (2.47–8.66) cm/year. The histological diagnosis was clear cell renal cell carcinoma (RCC) in seven patients, papillary in one and clear cell RCC with portions of sarcomatoid de‐differentiation in one; two patients had lymph node metastases and one had pulmonary metastases, and five had tumours of ≥T3.

CONCLUSIONS

The growth rate of large tumours is much higher than of small renal masses and most patients present with advanced disease. Thus, tumours of ≥4 cm seem not to be candidates for active surveillance but require immediate therapy. Further studies are warranted to determine the clinical relevance of progressive tumour growth and the underlying mechanisms.     

The impact of wait list body mass index changes on the outcome after liver transplantation

Obesity is associated with poor health outcomes in the general population, but the evidence surrounding the effect of body mass index (BMI) on postliver transplantation survival is contradictory. The aim of this study was to assess the impact of wait list BMI and BMI changes on the outcomes after liver transplantation. Using the Scientific Registry of Transplant Recipients, we compared survival among different BMI categories and examined the impact of wait list BMI changes on post‐transplantation mortality for patients undergoing liver transplantation. Cox proportional hazards multivariate regression was carried out to adjust for confounding factors. Among 38 194 recipients, underweight patients had a poorer survival compared with normal weight (HR = 1.3, 95% CI: 1.13–1.49). Conversely, overweight and mildly obese men experienced better survival rates compared with their lean counterparts (HR = 0.9, 95% CI: 0.84–0.96, and HR = 0.86, 95% CI: 0.79–0.93 respectively). Female patients gaining weight over 18.5 kg/m² while on the wait list showed improving outcomes (HR = 0.46, (95% CI: 0.28–0.76)) compared with those remaining underweight. This study supports the harmful impact of underweight on postliver transplant survival, and highlights the need for a specific monitoring and management of candidates with BMIs close to 18.5 kg/m². Obesity does not constitute an absolute contraindication to liver transplantation.     

Outcomes in the highest panel reactive antibody recipients of deceased donor kidneys under the new kidney allocation system

Since the institution of the new kidney allocation system in December 2014, kidney transplant candidates with the highest calculated panel reactive antibodies (cPRA) of 99‐100 have been transplanted at much higher rates. However, concerns have been raised that outcomes in these patients might be impaired due to higher immunological risk and longer cold ischemia times resulting from long‐distance sharing of kidneys. Here, we compare outcomes at the University of Wisconsin between study patients with cPRA 99‐100 and all other recipients of deceased donor kidneys transplanted between 12/04/2014 and 12/31/2015. All patients had at least 6 months post‐transplant follow‐up. The mean follow‐up was 13.9±3 months in cPRA ≥99% and 12.3±3.5 months in cPRA ≤98%. There was a total of 152 transplants, 25 study patients, and 127 controls. No statistically significant differences were found between the two groups in delayed graft function, rejection, kidney function, graft and patient survival, or infections. We conclude that transplanting the most highly sensitized patients with kidneys shared outside their local donation service areas is associated with excellent short‐term outcomes that are comparable to controls.     

Retroactive application of the new kidney allocation system to renal transplants performed in the ECD/SCD era

The kidney allocation system (KAS) aims to improve deceased donor kidney transplant outcomes by matching of donor allografts and kidney recipients using the kidney donor risk index (KDRI) and recipient estimated post‐transplant survival (EPTS) indices. In this single‐center study, KAS was retroactively applied to 573 adult deceased donor kidney transplants (2004–2012) performed in the extended criteria/standard criteria donor (ECD/SCD) era. Donor KDRI and recipient EPTS were calculated, and transplants were analyzed to identify KAS fits. These were defined as allocation of top 20% allografts to top 20% recipients and bottom 80% allografts to bottom 80% recipients. On retroactive calculation, 70.2% of all transplants fit the KAS. Transplants that fit the KAS had inferior 1‐ and 5‐yr patient survival (95.5% vs. 98.8%, p = 0.048, and 83.4% vs. 91.7%, p = 0.018) and similar 1‐ and 5‐yr graft survival compared to transplants that did not fit the KAS (91.3% vs. 94.1%, p = 0.276, and 72.7% vs. 73.9%, p = 0.561). While EPTS correlated with recipient survival (HR = 2.96, p < 0.001), KDRI correlated with both recipient (HR = 3.56, p < 0.001) and graft survival (HR = 3.23, p < 0.001). Overall, retroactive application of the KAS to transplants performed in the ECD/SCD era did not identify superior patient survival for kidneys allocated in accordance with the KAS.     

The impact of recurrence of primary glomerulonephritis on renal allograft outcome

Twenty‐yr patient and death‐censored graft survival of 348 kidney transplant recipients with primary glomerulonephritis (GN) and of 696 matched controls were 82.2% in GN patients and 75% in controls (p = 0.037) and 49.5% and 54%, respectively (p = 0.013). GN patients had a higher incidence of graft failure than controls even considering death as a competing risk (p = 0.004). In the GN group, graft survival of deceased and of living donor recipients was similar. At multivariate analysis, GN as primary disease (RR: 1.47), delayed graft function recovery (RR: 2.34), acute rejection (RR: 2.36), and any PRA positivity (RR: 1.01) were predictive of graft loss. GN recurred in 85 of 348 grafts (24.4%), and 43 were lost for recurrence. In non‐recurrent patients, graft survival at 20 yr was significantly better than in recurrent patients (59.4% vs. 24.4%, p = 0.000), but not different from that of controls (59.4 vs. 54%, p = 0.9). At multivariate analysis, young age at transplantation (RR: 0.97), shorter duration of dialysis (RR: 1.05 per each dialysis year), and graft from living donors (RR: 1.668) were independent predictors of recurrence. Patients with primary GN have reduced graft survival in comparison with controls, and this is mainly due to recurrence of original disease. However, the most frequent recurrence in living recipients does not compromise graft survival.     

The impact of in-situ balloon occlusion of the renal artery and hypothermic perfusion on renal blood flow

Summary Unilateral renal blood flow was evaluated in-situ in 13 dogs by cineangiodensitometry and microsphere distribution studies before and after intermittent balloon occlusion with and without hypothermic perfusion of one kidney. The contralateral kidney served as control. No significant difference in renal blood flow and vascular resistance was noted before, and 5, 30 and 60 minutes after unilateral intra-arterial manipulation. Compartmental flow distribution studies in 5 dogs revealed no evidence of alteration of intra-renal haemodynamics. In a clinical pilot study, unilateral renal blood flow measured by cineangiodensitometry showed no change of clinical significance 5 and 60 minutes after intraluminal balloon occlusion of the renal artery for 60 seconds.     

The impact of warm ischaemia on renal function after laparoscopic partial nephrectomy

Authors from Cleveland assessed the impact of warm ischaemia on renal function, using their large database of laparoscopic partial nephrectomies for tumour. While agreeing that renal hilar clamping is essential for precise excision of the tumour, and other elements of the operation, the authors indicate that warm ischaemia may potentially damage the kidney. However, they found that there were virtually no clinical sequelae from warm ischaemic of up to 30 min. They also found that advancing age and pre-existing renal damage increased the risk of postoperative renal damage. OBJECTIVE: To assess the effect of warm ischaemia on renal function after laparoscopic partial nephrectomy (LPN) for tumour, and to evaluate the influence of various risk factors on renal function. PATIENTS AND METHODS: Data were analysed from 179 patients undergoing LPN for renal tumour under warm ischaemic conditions, with clamping of the renal artery and vein. Renal function was primarily evaluated in two groups of patients: 15 with tumour in a solitary kidney, who were evaluated by serial serum creatinine measurements; and 12 with two functioning kidneys undergoing unilateral LPN, and evaluated by renal scintigraphy before and 1 month after LPN to quantify differential renal function. Also, in all 179 patients, mean serum creatinine data at baseline, 1 day after LPN, at hospital discharge, and at the last follow-up were provided as supportive evidence. Logistic regression analyses were used to assess the effect of various risk factors on renal function after LPN, i.e. patient age, baseline serum creatinine, tumour size, solitary kidney status, duration of warm ischaemia, pelvicalyceal suture repair, urine output and intravenous fluids during LPN. RESULTS: In the group of patients with a solitary kidney the mean warm ischaemia time was 29 min, kidney parenchyma excised 29%, and serum creatinine at baseline, discharge, the peak after LPN and at the last follow-up (mean 4.8 months) 1.3, 2.3, 2.8, and 1.8 mg/dL, respectively. One patient (6.6%) required temporary dialysis. In the second group, assessed by renal scintigraphy, the function of the operated kidney was reduced by a mean of 29%, commensurate with the amount of parenchyma excised. For all 179 patients, a combination of age > or = 70 years and a serum creatinine level after LPN of > or = 1.5 mg/dL correlated with a higher serum creatinine after LPN. On logistic regression, baseline serum creatinine and solitary kidney status were the only variables significant for serum creatinine status after LPN. CONCLUSIONS: The bloodless field provided by renal hilar clamping is important for precise tumour excision, pelvicalyceal suture repair and securing parenchymal haemostasis during LPN. However, renal hilar clamping causes warm ischaemia. These data indicate that the clinical sequelae of warm ischaemic renal injury of approximately 30 min are minimal. Advancing age and pre-existing azotaemia increase the risk of renal dysfunction after LPN, especially when the warm ischaemia exceeds 30 min.     

The impact of tumour location on the histological subtype of renal cortical tumours

OBJECTIVE: To determine whether the location of renal cortical tumours (RCTs) is a possible factor affecting tumour behaviour, by investigating whether exophytic vs a central location is associated with a difference in histological subtype distribution, as recognized prognostic factors for RCTs include size, stage, grade, and histological subtype. PATIENTS AND METHODS: Between 1 January 1996 and 1 June 2003, we evaluated 485 consecutive RCTs in 469 patients who had renal imaging studies and underwent either partial or radical nephrectomy at our institution. A radiologist and a urologist independently reviewed the imaging studies of all patients to determine exophytic vs central location. An exophytic lesion was defined as one that clearly both pushed out the renal contour and did not extend into the collecting system, hilum, or renal sinus. A lesion that did not meet these criteria was defined as a central lesion. Logistic regression analysis was used to determine if either type of lesion had a greater representation of any histological subtype. A two-tailed P < or = 0.05 was considered to indicate significance. RESULTS: Of the 485 RCTs, 171 (35%) were exophytic and 314 (65%) were central, while 308 (64%) were clear cell and 177 (36%) were non-clear cell tumour histology. Of the exophytic lesions, 52.0% were clear cell, while 69.7% of central lesions were clear cell (P < 0.001). Conversely, 71.1% of clear cell tumours were central, while 53.7% of non-clear cell tumours were central (P = 0.003). After controlling for size and stage, tumour location remained associated with histological subtype (P = 0.003). CONCLUSIONS: Exophytic lesions are significantly more likely than central lesions to be non-clear cell tumours, and clear cell tumours are significantly more likely than non-clear cell tumours to be central. As studies indicate that the clear cell histological subtype portends a worse prognosis than the non-clear cell subtype, our results imply that tumour location affects the prognosis in RCTs, with exophytic lesions having a better prognosis than central lesions. This result may have important implications for physicians and patients when planning partial vs radical nephrectomy by either open or minimally invasive techniques.     

Experience with the Wujciak-Opelz allocation system in a single center: an increase in HLA-DR mismatching and in early occurring acute rejection episodes

The present single-center, retrospective study was undertaken to assess the impact of the Wujciak-Opelz allocation system (XCOMB), currently used within Eurotransplant for renal allografts, on the incidence of early occurring rejection episodes (RE). Implementation of the system resulted in an increase of HLA-DR mismatches (MM), while the incidence of HLA-A + B + DR MM remained unchanged. During the 1st post-transplant month, the total number of RE, expressed per patient-months, increased by 64 % (0.326 vs 0.199, P = 0.007); when considering only severe and irreversible RE, the increase was 76 % (0.158 vs 0.090, P = 0.011). In contrast, from the 2nd to the 12th post-transplant month, the incidence of RE, regardless of severity, was similar before and after implementation of XCOMB. As early occurring RE have detrimental effects on long-term graft outcome, these observations, if confirmed on a larger scale, would justify changes in the allocation algorithm. Received: 13 February 1998 Received after revision: 29 April 1998 Accepted: 20 May 1998     

Access to the waiting list and to kidney transplantation for people living with HIV: A national registry study

We compared access to a kidney transplantation (KT) waiting list (WL) and to KT between people living with HIV (PLHIV) and HIV‐uninfected controls. Using the REIN (the national Renal Epidemiology and Information Network registry), we included all PLHIV initiating dialysis in France throughout 2006‐2010 and HIV‐uninfected controls matched for age, sex, year of dialysis initiation, and the existence of a diabetic nephropathy. Patients were prospectively followed until December 2015. We used a competitive risk approach to assess the cumulative incidence of enrollment on WL and of KT, with death as a competing event (subdistribution hazard ratio adjusted on comorbidities, asdHR). There were 255 PLHIV in the REIN (median age 47 years) of whom 180 (71%) were also found in the French Hospital Database on HIV (FHDH‐ANRS CO4) including 126 (70%) known to be on antiretroviral therapy with HIV viral suppression (VS). Five years after dialysis initiation, 65%, and 76%, of treated PLHIV with VS, and of HIV‐uninfected controls were enrolled on a WL (asdHR 0.68; 95% CI 0.50‐0.91). Access to KT was also less frequent and delayed for treated PLHIV with VS (asdHR 0.75, 95% CI, 0.52‐1.10). PLHIV continue to face difficulties to access KT.