Reassessing the Significance of Intimal Arteritis in Kidney Transplant Biopsy Specimens

Intimal arteritis (the presence of v-lesions) in kidney transplant biopsy specimens is believed to have major prognostic and diagnostic significance. We assessed the relationship of v-lesions to prognosis in 703 indication biopsy specimens and used microarray-based molecular tests to re-examine the relationship of v-lesions to rejection. v-Lesions were noted in 49 specimens (7%) and were usually mild (v1). The presence of v-lesions had no effect on graft survival compared with the absence of v-lesions. Pathologists using current conventions almost always interpreted v-lesions as reflecting T cell–mediated rejection (TCMR), either pure or mixed with antibody-mediated rejection (ABMR). The molecular scores questioned the conventional diagnoses in 29 of 49 specimens (59%), including ten that were conventional TCMR with no molecular rejection and nine that were conventional TCMR mixed with pure ABMR molecularly. The presence of tubulointerstitial inflammation (i-t) meeting TCMR criteria allowed subclassification of v-lesion specimens into 21 i-t-v-lesion specimens and 28 isolated v-lesion specimens. Molecular TCMR scores were positive in 95% of i-t-v-lesion specimens but only 21% of isolated v-lesion specimens. Molecular ABMR scores were often positive in isolated v-lesion biopsies (46%). Time of biopsy after transplantation was critical for understanding isolated v-lesions: most early isolated v-lesion specimens had no molecular rejection and were DSA negative, whereas most isolated >1 year after transplantation had positive DSA and ABMR scores. Therefore, v-lesions in indication biopsy specimens do not affect prognosis and can reflect TCMR, ABMR, or no rejection. Time after transplantation, DSA, and accompanying inflammation provide probabilistic basis for interpreting v-lesions.     

End stage polycystic kidney disease: indications and timing of native nephrectomy relative to kidney transplantation

PURPOSE: We evaluated the indications for and outcome of pre-transplant, concomitant and post-transplant native nephrectomy in patients with end stage polycystic kidney disease (PCKD). MATERIALS AND METHODS: The records of 32 patients were retrospectively reviewed using the electronic database at our institution. RESULTS: Between January 1992 and December 2002, 171 patients with end stage PCKD received a kidney transplant at University of California-San Francisco. A total of 32 patients (18.7%) underwent pre-transplant (7, group 1), concomitant (16, group 2) or post-transplant (9, group 3) native nephrectomy. Of these patients 25 underwent bilateral nephrectomy. Median followup was 18 months. Indications for nephrectomy were hematuria, a renal mass and chronic pain in group 1, lack of space in group 2 and urinary tract infection in group 3. Mean operative time +/- SEM was 231 +/- 14, 370 +/- 24 and 208 +/- 14 minutes in groups 1 to 3, respectively (p = 0.001). Mean intraoperative blood loss was 533 +/- 105, 573 +/- 155 and 522 +/- 181 ml in groups 1 to 3, respectively (p not significant). Two group 2 patients required blood transfusions. Postoperative complications requiring surgical intervention included wound dehiscence in group 1 and abdominal bleeding in group 3. Mean hospital stay was comparable among groups 1 to 3 at 7 +/- 0.7, 8.6 +/- 1.2 and 6.3 +/- 0.6 days, respectively (p not significant). At 3 months mean serum creatinine was not significantly different between groups 2 and 3 at 1.3 +/- 0.1 and 1.5 +/- 0.2 mg/dl, respectively. CONCLUSIONS: Unilateral or bilateral nephrectomy for PCKD at transplantation is safe in terms of postoperative patient morbidity and graft function. We perform concomitant native nephrectomy when indicated, preferably in recipients of living donor kidney transplants.     

Is lower pole caliceal anatomy predictive of extracorporeal shock wave lithotripsy success for primary lower pole kidney stones?

PURPOSE: The management of lower pole kidney stones is controversial. We examined whether lower pole caliceal anatomy could predict the success of extracorporeal shock wave lithotripsy of primary lower pole kidney stones 20 mm. or less. MATERIALS AND METHODS: From December 1997 to June 2001, 246 adults with a single, 20 mm. or less radiopaque lower pole renal stone were treated with the Doli 50 lithotriptor (Dornier Medical Systems, Marietta, Georgia) while under general anesthesia. Of the 246 patients 190 (77%) had excretory urography available for review. Lower pole infundibular length and width, lower pole infundibulopelvic angle and caliceal-pelvic height were measurable on 161 (85%), 129 (68%), 128 (67%) and 163 (86%) excretory urograms, respectively. Extracorporeal shock wave lithotripsy was considered a failure if residual stone fragments remained after 1 month, or an auxiliary procedure or re-treatment was required.RESULTS The overall stone-free rate was 78% (32 of 41) for stones 5 mm. or less, 73% (98 of 135) for stones 6 to 10 mm., 43% (22 of 51) for stones 11 to 15 mm. and 30% (7 of 19) for stones 16 to 20 mm. in maximum linear dimension. The stone-free rates grouped according to stone surface area were 76% (48 of 63 stones) for stone surface area 25 mm.2 or less, 69% (97 of 141) for 26 to 100 mm.2 and 33% (14 of 42) for 101 to 400 mm.2. Caliceal anatomy was not predictive of success even with stones grouped as 10 or less or 11 to 20 mm. Grouping patients with favorable (lower pole infundibulopelvic angle 70 degrees or greater, lower pole infundibular length 30 mm. or less and lower pole infundibular width greater than 5 mm.) versus unfavorable (70 degrees or less, greater than 30 mm. and 5 mm. or less, respectively) anatomy was also not predictive of success. CONCLUSIONS: On the Doli 50 machine stone size rather than caliceal anatomy is predictive of treatment outcome. Initial treatment failures with this machine should be managed by alternative endoscopic procedures if necessary rather than by repeat shock wave lithotripsy.     

肾下盏肾盂夹角对冲击波碎石治疗肾下盏结石效果的影响

目的探讨肾下盏肾盂夹角对SWL治疗肾下盏结石效果的影响. 方法 1998年1月～2004年1月采用冲击波碎石治疗肾下盏结石263例,选择单发结石直径在0.5 cm～1.5 cm之间、肾下盏长度＜3 cm以及盏颈宽度≥5mm的42例作为研究对象, 其中肾下盏肾盂夹角≥90°者27例, 肾下盏肾盂夹角＜90°者15例. 结果 3个月后复查,42例患者总结石排净率为76%,肾下盏肾盂夹角≥90°的结石排净率为85.2%, 肾下盏肾盂夹角＜90°的结石排净率为46.7%, 两组比较有统计学差异(P＜0.05). 结论肾下盏肾盏夹角对SWL治疗肾下盏结石的疗效有影响,肾下盏肾盂夹角≥90°者明显优于肾下盏肾盂夹角＜90°者.     

多囊肾术前不切原肾同种异体尸肾移植11例报告

目的探讨多囊肾尿毒症患者肾移植术前小切多囊肾对肾移植的影响。方法对11例移植术前不切多囊肾尿毒症患者，在成功进行肾脏移植后进行经验总结。追踪术后移棺肾肾功能恢复及术后3年人／移植肾存活率和术后1年原肾体积及血尿变化情况。结果11例移植术前小切多囊肾的尿毒症患者，术后移植肾肾功能均能顺利恢复，占100％。人／移植肾3年存活率100％，移植后原肾体积逐步缩小，12个月内明显缩小20％-45％，血尿逐渐消失。2例术后因原多囊肾严重感染而手术切除（18％）。结论多囊肾尿毒症患者肾移植术前不切原病变肾也能收到满意的移植效果。     

The effect of treatment strategy on stone comminution efficiency in shock wave lithotripsy

PURPOSE: The comminution of kidney stones in shock wave lithotripsy (SWL) is a dose dependent process caused primarily by the combination of 2 fundamental mechanisms, namely stress waves and cavitation. The effect of treatment strategy with emphasis on enhancing the effect of stress waves or cavitation on stone comminution in SWL was investigated. Because vascular injury in SWL is also dose dependent, optimization of the treatment strategy may produce improved stone comminution with decreased tissue injury in SWL. MATERIALS AND METHODS: Using an in vitro experiment system that mimics stone fragmentation in the renal pelvis spherical BegoStone (Bego USA, Smithfield, Rhode Island) phantoms (diameter 10 mm) were exposed to 1,500 shocks at a pulse repetition rate of 1 Hz in an unmodified HM-3 lithotripter (Dornier Medical Systems, Kennesaw, Georgia). The 3 treatment strategies used were increasing output voltage from 18 to 20 and then to 22 kV every 500 shocks with emphasis on enhancing the effect of cavitation on medium fragments (2 to 4 mm) at the final treatment stage, decreasing output voltage from 22 to 20 and then to 18 kV every 500 shocks with emphasis on enhancing the effect of stress waves on large fragments (greater than 4 mm) at the initial treatment stage and maintaining a constant output voltage at 20 kV, as typically used in SWL procedures. Following shock wave exposure the size distribution of fragments was determined by the sequential sieving method. In addition, pressure waveforms at lithotripter focus (F2) produced at different output settings were measured using a fiber optic probe hydrophone. RESULTS: The rate of stone comminution in SWL varied significantly in a dose dependent manner depending on the treatment strategies used. Specifically the comminution efficiencies produced by the 3 strategies after the initial 500 shocks were 30.7%, 59% and 41.9%, respectively. After 1,000 shocks the corresponding comminution efficiencies became similar (60.2%, 68.1% and 66.4%, respectively) with no statistically significant differences (p = 0.08). After 1,500 shocks the final comminution efficiency produced by the first strategy was 88.7%, which was better than the corresponding values of 81.2% and 83.5%, respectively, for the other 2 strategies. The difference between the final comminution efficiency of the first and second strategies was statistically significant (p = 0.005). CONCLUSIONS: Progressive increase in lithotripter output voltage can produce the best overall stone comminution in vitro.     

IN VITRO STUDY OF ULTRASOUND BASED REAL-TIME TRACKING OF RENAL STONES FOR SHOCK WAVE LITHOTRIPSY: PART 1

PURPOSE: We developed a real-time tracking system for renal stones that decreases the number of shock waves and treatment time of shock wave lithotripsy. MATERIALS AND METHODS: Ultrasound images were analyzed to identify the renal stones. A computer software module for ultrasound image processing was developed to monitor stone location instantaneously. Another computer software module controlled generator movement in real time for tracking the stone. We used 13 ultrasound stone trajectories recorded from patients to test the system in vitro. Two tests were established to verify tracking system reliability. One test focused on improvement in the coincidence ratio, which denotes the matching extent of the stone within the effective focal area. The other test focused on improvement in the efficiency ratio, that is a decrease in the number of shocks for stone fragmentation. For each recorded stone trajectory 2 experiments were done under tracking and nontracking conditions. RESULTS: The average coincidence and efficiency ratios plus or minus standard deviation were 79.6% +/- 9.8% and 45.0% +/- 12.7% without tracking, and 97.0% +/- 3.0% and 85.5 +/- 6.8% with tracking, respectively. All tests were statistically significant (paired t test p <0.01). CONCLUSIONS: An ultrasound based real-time tracking system proved to be significantly helpful for in vitro lithotripsy. It appears that the tracking system may greatly decrease the number of shocks and treatment time for renal stones.     

Outcomes and Utilization of Kidneys from Deceased Donors with Acute Kidney Injury

Utilization and long-term outcomes of kidneys from donors with elevated terminal serum creatinine (sCr) levels have not been reported. Using data from the Scientific Registry of Transplant Recipients from 1995 to 2007, recipient outcomes of kidneys from adult donors were evaluated stratified by standard criteria (SCD; n = 82 262) and expanded criteria (ECD; n = 16 978) donor type and by sCr ≤1.5, 1.6–2.0 and >2.0 mg/dL. Discard rates for SCDs were ascertained. The relative risk of graft loss was similar for recipients of SCD kidneys with sCr of 1.6–2.0 and >2.0 mg/dL, compared to ≤1.5 mg/dL. For ECD recipients, the relative risk of graft failure significantly increased with increasing sCr. Of potential SCDs, the adjusted risk of discard was higher with sCr >2.0 mg/dL (adjusted odds ratio [AOR] 7.04, 95% confidence interval [CI] 6.5–7.6) and 1.6–2.0 mg/dL (AOR 2.7; CI 2.5–2.9) relative to sCr ≤1.5 mg/dL. Among potential SCDs, elevated terminal creatinine is a strong independent risk factor for kidney discard; yet, when kidney transplantation is performed elevated donor terminal creatinine is not a risk factor for graft loss. Further research is needed to identify safe practices for the optimal utilization of SCD kidneys from donors with acute kidney injury.     

Clinical efficacy of a combination pneumatic and ultrasonic lithotrite

PURPOSE: A new combination pneumatic/ultrasonic intracorporeal lithotriptor has been developed for percutaneous applications. It combines the stone clearing efficiency of an ultrasonic device with the fragmentation strength of a pneumatic probe into a single handpiece. We present our early clinical experience with this device in a prospective, randomized comparison a combination pneumatic/ultrasound lithotrite and standard ultrasonic lithotripsy. MATERIALS AND METHODS: A total of 20 consecutive patients undergoing percutaneous nephrolithotomy for symptomatic calculi were randomized to receive stone fragmentation and removal using a standard ultrasonic device or a new combination pneumatic/ultrasonic unit. Stone location and burden were assessed before the operative procedure. The stone clearance rate in mm.2 per minute was calculated for the 2 devices. Complications and stone-free rates were compared in the 2 groups. RESULTS: There were no significant differences in stone location and composition in the 2 groups of patients. Average time required for complete stone clearance was considerably less for the combination device (21.1 versus 43.7 minutes, p = 0.036). The opposite was true for the average rate of stone clearance in mm.2 per minute, in that the standard ultrasonic device could clear 16.8 versus 39.5 mm.2 per minute for the combination unit (p = 0.028). Stone-free and complications rates were slightly superior for the combination device but it was likely attributable to patient factors. CONCLUSIONS: The combination pneumatic/ultrasonic lithotrite is capable of disintegrating and extracting stone material at a more rapid rate than standard ultrasonic devices. Moreover, stone-free and complication rates appear to be slightly superior with the combination unit. This new combination pneumatic/ultrasonic device appears to be efficacious and safe for removing large renal calculi.     

Selective, concurrent bilateral nephrectomies at renal transplantation for autosomal dominant polycystic kidney disease

PURPOSE: An algorithm was developed for performing bilateral nephrectomies for specific indications before or at renal transplantation in patients with autosomal dominant polycystic kidney disease. Outcomes for the living donor arm of the algorithm are reported. MATERIALS AND METHODS: Patients with autosomal dominant polycystic kidney disease and end stage renal disease were evaluated for transplantation. Patients with recurrent pyelonephritis, hemorrhage, pain, early satiety or kidneys that extended into the true pelvis underwent bilateral nephrectomies. Bilateral nephrectomies with concurrent renal transplantation were performed if a living renal donor was identified. If no living donor was identified, pre-transplantation bilateral nephrectomies were done and the patients were listed for cadaveric donor renal transplantation. The living renal donor arm of the algorithm was evaluated by comparing certain parameters for 15 and 17 patients with autosomal dominant polycystic kidney disease who underwent pre-transplantation and concurrent bilateral nephrectomies, respectively, including patient and graft survival, delayed graft function, graft function, length of stay for each surgery, transfusions and complications. RESULTS: No deaths, graft failures or delayed graft function occurred. In the delayed renal transplant group median time from nephrectomy to living donor transplantation was 124 days. Serum creatinine at discharge home and 1 year after transplantation for the pre-transplantation nephrectomy cohort was 2.0 and 1.3 mg/dl, respectively. Seven of the 17 patients with concurrent nephrectomy underwent transplantation before starting renal replacement therapy. A longer mean total hospital stay in the pre-transplantation nephrectomy cohort was the only statistically significance outcome variable. CONCLUSIONS: Selective bilateral nephrectomies at living donor renal transplantation results in decreased total length of stay without compromising patient or graft outcomes and it allows preemptive renal transplantation. Concurrent nephrectomy is safe and it further validates the algorithm for selective, concurrent bilateral nephrectomies for patients with autosomal dominant polycystic kidney disease who undergo living donor renal transplantation.     

Stone formation is proportional to papillary surface coverage by Randall's plaque

PURPOSE: Randall's plaques are common in calcium oxalate (CaOx) stone formers (SF). Plaque coverage correlates directly with urine calcium excretion and inversely with urine volume. We hypothesize that plaque coverage should increase proportionally with increasing stone number. We measured plaque areas in idiopathic CaOx stone formers and nonstone formers (NSF), and identified significant relationships with quantified stone histories. MATERIALS AND METHODS: A total of 13 SFs and 4 control NSFs underwent nephroscopic papillary mapping with representative still images and MPEG (Moving Pictures Experts Group) movies used to identify plaque and papillary borders. Stone histories were obtained through patient interviews, and from medical records and radiographs. The relationship of plaque coverage to clinical stone events was assessed by general multivariate linear modeling. Log transformation normalized the distribution of percent plaque coverage and stone number. RESULTS: Plaque surface area in SFs differed significantly from that in NSFs (p <0.0001). The duration of stone disease and the log transformed percent plaque coverage correlated significantly with the number of stones (0.677 and 0.620, p = 0.003 and 0.008, respectively). On multivariate analysis and correcting for the duration of stone disease total percent plaque coverage correlated significantly with the number of stones (R = 0.496, p = 0.05). Disease duration and plaque coverage did not correlate significantly (p = 0.257). CONCLUSIONS: Percent plaque coverage directly correlates with the number of stones formed even when corrected for the duration of stone disease. However, plaque coverage does not correlate with the duration of stone disease. These results support the hypothesis that the pathogenesis of CaOx stones begins with Randall's plaques.     

Baseline living‐donor kidney volume and function associate with 1‐year post‐nephrectomy kidney function

Living donors may develop kidney dysfunction more often than equally healthy populations. The purpose of this study was to determine whether computed tomography‐assessed remaining kidney volume indexed to body surface area (RKV/BSA) was associated with 1‐year post‐nephrectomy renal function independent of baseline renal function. Using multivariable regression, we modeled 1‐year estimated glomerular filtration rate (eGFR) and eGFR <60 mL /min/1.73 m² and considered pre‐determined baseline eGFR subgroups in 151 consecutive donors. Mean ± SD baseline age, eGFR, RKV, BSA, and RKV/BSA were 38 ± 11 years, 97 ± 16 mL/min/1.73 m², 153 ± 29 mL, 1.9 ± 0.2 m², and 80.0 ± 12.8 ml/m², respectively; 50% were female and 94% were white. Mean baseline eGFR was greater with increasing RKV/BSA tertiles (92 ± 14, 97 ± 16, 107 ± 16 mL/min/1.73 m²; P < 0.001). Post‐nephrectomy eGFR remained separated by RKV/BSA tertiles. At baseline, each SD greater RKV/BSA and eGFR was independently associated with higher adjusted 1‐year eGFR by 2.4 and 9.2 mL/min/1.73 m². Each SD greater age associated with 2.2 mL/min/1.73 m² lower adjusted 1‐year eGFR. Adjusted odds of 1‐year eGFR <60 increased significantly for donors with RKV/BSA <80 mL/m². With baseline eGFR <90, probability of 1‐year eGFR <60 increased to >80% with decreasing RKV/BSA values below 80 mL/m². Those with baseline eGFR >100 rarely developed 1‐year eGFR <60 if RKV/BSA remained >60 mL/m². RKV/BSA independently associated with 1‐year eGFR <60, especially with lower baseline eGFRs. Additional studies should evaluate the predictive utility of this measure and its potential role in donor evaluations and informed consent.     

Limitations of laparoscopy for bilateral nephrectomy for autosomal dominant polycystic kidney disease

PURPOSE: We retrospectively studied outcomes following bilateral hand assisted laparoscopic nephrectomy. MATERIALS AND METHODS: We retrospectively reviewed the charts of 18 patients with symptomatic autosomal dominant polycystic kidney disease who underwent bilateral hand assisted laparoscopic nephrectomy. Preoperative radiographic imaging was reviewed retrospectively to determine kidney size based on an ellipsoid shape. A visual analog pain scale with scores of 0 to 10 to assess pain related to autosomal dominant polycystic kidney disease was measured preoperatively and postoperatively. RESULTS: Average patient age was 48.2 years (range 30 to 64). Of the patients 14 successfully underwent bilateral hand assisted laparoscopic nephrectomy, while 4 required open conversion. A total of 16 patients underwent nephrectomy for pain and 2 underwent surgery for frequent recurrent symptomatic urinary tract infections. All patients except 1 underwent renal transplantation before bilateral nephrectomy. There was a significant difference in the volume of the right and left kidneys between the hand assisted laparoscopic and open groups (mean +/- SD 1,043 +/- 672 and 1,058 +/- 603.8 vs 4,052 +/- 548 and 3,592 +/- 1,752 cm(3), p <0.001 and 0.06 respectively). There were 5 complications, including wound infection and protracted ileus in 2 patients each, and incisional hernia in 1. In addition, the difference in mean preoperative and postoperative visual analog pain scores was statistically significant (6.9, range 3 to 10 and 0.5, range 0 to 2, p <0.05). CONCLUSIONS: Bilateral laparoscopic hand assisted nephrectomy is a safe and reliable option in patients requiring removal of the 2 kidneys in a single setting. Rather than performing staged nephrectomies, hand assisted laparoscopic nephrectomy allows the single administration of general anesthesia and provides effective relief of bothersome symptoms in patients with symptomatic autosomal dominant polycystic kidney disease. This procedure is safe in patients with renal transplants. Patients with massive polycystic kidneys with a kidney volume of greater than 3,500 cc are at increased risk for open conversion and they may have improved outcomes if open nephrectomy is attempted from the outset.     

Grandparent donors in paediatric renal transplantation

The outcome of transplantation from grandparent donors in comparison with parental donors in paediatric renal transplantation was evaluated in 53 living related donor (LRD) transplantations performed between January 1996 and August 2003. The donor in 13 cases (25%) was a grandparent (Gpar group), and the remaining donors formed the parent group (Par group). The median age of recipients in the Gpar group was 2.75 (1.7–10.6) years and in the Par group was 12.75 (2.4–22) years (P<0.0001). There was no evidence of a difference in patient and graft survival, glomerular filtration rate (GFR) after transplantation, or the number of biopsy proven episodes of rejection between the groups. Doses of prednisolone in the first year following transplantation were greater in recipients from Gpar donors, but the other immunosuppression doses were similar. The median age of donors in the Gpar group was 56 (50–67) years and in the Par group was 41 (27–58) years (P<0.0001). There was no evidence of a difference between the two donor groups in mean creatinine clearance at last follow-up. There were two major donor complications in the Gpar group and one in the Par group. There was no evidence that the length of stay differed between the two groups in either the donors or recipients. These results support the use of carefully selected healthy grandparents as LRDs in children. This option potentially allows for the use of parent donors for a subsequent transplantation.     

En bloc kidney transplant from an 18-month-old donor to an adult recipient: Case report and literature review

INTRODUCTIONThere is an ever-increasing need for organ donations globally. Paediatric kidney transplantation into adult recipients is a well-recognised technique to expand the donor pool. The transplantation can be done either via en bloc kidney transplant (EBKT) or as single kidney transplantation (SKT).PRESENTATION OF CASEAn EKBT from a 18-month-old (15 kg) male patient was transplanted in a 35-year old, 85 kg male with end stage renal failure (ESRF), secondary to Focal Segmental Glomerulosclerosis (FSGS) on haemodialysis. Post-operative recovery was uneventful. Immuno-suppressant drugs used were tacrolimus, basiliximab and prednisolone. Doppler ultrasound scans performed post-operatively showed normal renal resistive indices in both kidneys. Serum creatinine decreased from 1200 to 170 μmol/L 57 with eGFR improving from 4 to 38 mL/min/1.73 m² at four weeks post-transplant.DISCUSSIONGiven the low incidence of paediatric donors, EBKTs are relatively uncommon and subsequently published series tend to be centre specific with small numbers. The graft survival rates tell us that paediatric kidney donors should not be considered as marginal transplants. The difficulty is in determining when it is more appropriate to perform a paediatric EBKT as opposed to splitting and performing two SKT. Unfortunately there are no widely accepted guidelines to direct clinicians.CONCLUSIONThis case report highlights the first EKBT performed at our institution. The current literature demonstrates that paediatric donors are excellent resources that should be procured whenever available.