Compensatory responses to nephron deficiency: Adaptive or maladaptive?

Compensatory renal growth is a characteristic adaptation to reduced renal mass that appears to recapitulate the normal pattern of maturation of the kidney during the postnatal period. Hypertrophy of tubules (predominantly the proximal tubule) and glomeruli is accompanied by increased single nephron glomerular filtration rate and tubular reabsorption of sodium. We propose that the very factors, which contribute to the increase in growth and function of the renal tubular system, are, in the long term, the precursors to the development of hypertension in those with a nephron deficit. The increase in single nephron glomerular filtration rate is dependent on multiple factors, including reduced renal vascular resistance associated with an increased influence of nitric oxide, and a rightward shift in the tubuloglomerular feedback curve, both of which contribute to the normal maturation of renal function. The increased influence of nitric oxide appears to contribute to the reduction in tubuloglomerular feedback sensitivity and facilitate the initial increase in glomerular filtration rate. The increased single‐nephron filtered load associated with nephron deficiency may promote hypertrophy of the proximal tubule and so increased reabsorption of sodium, and thus a rightward shift in the pressure natriuresis relationship. Normalization of sodium balance can then only occur at the expense of chronically increased arterial pressure. Therefore, alterations/adaptations in tubules and glomeruli in response to nephron deficiency may increase the risk of hypertension and renal disease in the long‐term.     

高选择性肾动脉分支阻断与全阻断下腹腔镜保留肾单位手术疗效及肾功能对比

目的 探讨肾动脉主干阻断(main renal artery clamping,MRAC)与高选择性肾段动脉分支阻断(selective segmental renal artery clamping, SSRAC)下行腹腔镜保留肾单位手术(laparoscopic nephron sparing surgery, LNSS)的临床效果及安全性评价。方法 回顾性分析2017年10月至2018年10月收治的T1期局限性肾肿瘤患者84例,其中行SSRAC下LNSS 42例(S组),行MRAC下LNSS 42例(M组)。比较2种手术方法的手术时间、术中失血量、术中热缺血时间、术后住院时间、切缘阳性率;术前术后SCr、BUN;术中、术后并发症发生率等。结果 所有手术顺利完成,无手术切缘阳性者,无术中中转为MRAC者。S组手术时间、术中失血量较M组增加,差异有统计学意义(P<0.05),2组术中热缺血时间、术后引流量、术后住院时间等差异无统计学意义(P>0.05);2组术前SCr、BUN水平差异无统计学意义(P>0.05),术后1 d血SCr、BUN水平较术前显著升高,S组术后1 d SCr、BUN显著低于M组(P<0.05);2组患者术中术后并发症发生率差异无统计学意义(P>0.05)。结论 SSRAC是新的肾动脉阻断技术,应用于LNSS患者治疗效果显著、安全性高,且对肾脏功能影响小,本研究尚需要大样本数据支持。     

Significance of margin in nephron sparing surgery for renal cell carcinoma of 4 cm or less

Background Current surgical practice for nephron sparing surgery allows at least 1 cm margin of normal tissue around the tumour. However, recent studies show that the width of the margin is not important, even simple enucleation is as effective as partial nephrectomy. We explored whether margin size has significant impacts on clinical outcomes in nephron sparing surgery for renal cell carcinoma of 4 cm or less. Methods Between 1998 and 2006, 115 patients with sporadic, pathologically confirmed, renal cell carcinoma 4 cm or less （Tla） and normal contralateral kidney were treated by nephron sparing surgery using a margin less than 5 mm. The surgical margin status was evaluated from frozen and permanent paraffin sections. Results Mean and median tumour diameter were 3.3 cm and 3.5 cm （range 1.0-4.0）. The mean margin width was 2.2 mm （median 2.0, range 0-6）. In addition, 114 cases had margins 5 mm or less （99.1%）, 97 cases （84.3%） had margin 3 mm or less, and 26 cases had margin zero （22.6%）. None of the patients had positive surgical margins. No patients died during follow-up （mean 65 months）. There were no any major surgical complications and no distant metastasis was detected. Local recurrence was detected in one case （0.9%） at a different site of the kidney. Conclusions For early localized renal cell carcinoma of 4 cm or less, as long as tumour is completely excised, the size of margin in nephron sparing surgery is not important. Nephron sparing surgery with 5 mm margin is enough for tumour control. It provides excellent renal function preservation, favourable long term progression free survival and is not associated with an increased risk of local recurrence.     

Chronologically different impacts of immunologic and non-immunologic risk factors on renal allograft function

INTRODUCTION: Upon analysis of the risk factors affecting renal graft survival and function, the time-dependent effects of each risk factor should be differentiated from their net effects. To evaluate the chronologically different impacts of risk factors on graft renal function, we reviewed 390 recipients who received a kidney from 1-haplotype-matched living-related donors. MATERIALS AND METHODS: Until 5-yr post-transplantation (TX), yearly serum creatinine (Scr), 24-h urinary excretion of protein, and their yearly changes were compared by the episodes of acute rejection within 1 yr, the kidney weight to recipient body weight (KW/BW) ratio, the donor/recipient (D/R) age ratio, and the D/R gender pairing. The Kaplan-Meier method, Cox proportional hazard model, ANOVA, and repeated measures ANOVA were each applied for different purposes. RESULTS: Only the episodes of acute rejection were a significant risk factor affecting graft survival. The episodes of acute rejection, KW/BW ratio, D/R age ratio, and D/R gender pairing consistently and independently had significant influences on Scr. Recipients having the lowest KW/BW ratio (first quartile) or the highest D/R age ratio (fourth quartile) had rapid increments of Scr after 4-yr post-TX. After 3-yr post-TX, there were significant correlations between the number of non-immunologic risk factors present and the yearly changes in Scr. CONCLUSIONS: Non-immunologic factors had a detrimental effect on renal graft function, especially after 3-yr post-TX. If immunologic risks seem to be similar, size matching, age, and gender pairing should be considered for better long-term graft function in renal TX recipients.     

Sensitivity of Na K adenosine triphosphatase activity in various structures of the rat nephron: studies with adrenalectomy

Abstract. Proximal and distal tubular segments of the subcapsular nephron and segments of the ascending limb of Henle's loop were dissected out freehand from lyophilized kidney section of male rats after bilateral adrenalectomy. The microdissected nephron structures were weighed with a quartz fibre balance. Na K ATPase was determined by analyzing the total ATPase and the Mg ATPase in dissected material. As soon as 6 h after adrenal enucleation a 65% reduction of Na K ATPase activity in the ascending limb of Henle's loop and a 81 % diminution in the distal convoluted portion were detected; 24 h after adrenalectomy an additional reduction of the transport enzyme in the proximal convoluted portion was simulated by an enzyme activity increase in the sham-operated controls. In contrast to previous authors working with homogenate or membrane fraction of the whole kidney, the present quantitative histochemical results indicate a close adaptation of Na K ATPase to the altered sodium transport in rat kidney after adrenalectomy.     

新生儿肾脏输尿管膀胱的组织学观察

本文观察了新生儿肾脏12例、输尿管10例和膀胱7例,测量了肾单位各段的最大直径,计算出均数与标准差。结果表明:1.新生儿肾的发育程度与体重有关,新生儿的体重从1400～3200g,肾皮质浅层的生肾区逐渐变薄、消失,生肾区内的肾小体呈S形,肾小管为实心细胞团;肾皮质的肾小体从5～6代逐渐增加到10多代,每个肾小体的体积逐渐增大,肾小管管径逐渐增粗,致密斑的细胞由矮变高;球外系膜细胞逐渐增多;集合管上皮细胞由深染的立方细胞变成淡染的柱状细胞。2.皮质深层的肾小体已分化成熟,而浅层的较幼稚。3.出生后存活时间越长,肾单位各段的直径越大,表明出生后肾继续发育。4.细段上皮细胞为立方形。     

Trends in the use of of nephron-sparing surgery (NSS) at an Australian tertiary referral centre: an analysis of surgical decision-making using the R.E.N.A.L. nephrometry scoring system

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Nephron‐sparing surgery (NSS) is increasingly recognised as a preferred form of management for the incidentally detected small renal mass (SRM). Within the context of equivalent oncological outcomes, patients treated by NSS may have a survival advantage over those treated by radical nephrectomy (RN) through a reduced risk of chronic kidney disease and its associated cardiac morbidity. Despite this, according to Medicare data from the USA, a disproportionate number of patients with SRMs continue to be treated with RN instead of NSS. Similar data from Australia are not yet available. The present study explores the evolving management of SRMs at an Australian tertiary centre over a 5‐year period. It utilises the R.E.N.A.L. Nephrometry Score to assess how lesion complexity has influenced surgical decision‐making and charts the increasing use of NSS in the management of low‐complexity renal masses at our centre.

OBJECTIVE

• ? To examine recent trends in the use of nephron‐sparing surgery (NSS) at our centre. Specifically, we sought to examine the process of surgical decision‐making by applying the R.E.N.A.L. nephrometry scoring system to assess the complexity of lesions for which surgery was undertaken.

PATIENTS AND METHODS

• ? We performed a retrospective review of renal masses treated by surgery from January 2005 to December 2009, including 79 RN and 70 NSS.
• ? CT images were available for analysis in 50 patients within each group.
• ? Lesions were scored on the basis of their complexity using the R.E.N.A.L. nephrometry scoring system developed by Kutikov and Uzzo.

RESULTS

• ? There was no difference in age between patients undergoing RN and NSS (median age 61 vs 60 years).
• ? RN was performed for significantly larger lesions (mean [sd ] 68 [9] vs 29 [2] mm, P < 0.05) of predominantly moderate and high complexity (12% low, 56% moderate, 32% high).
• ? NSS was primarily used for low‐complexity lesions, but included four (8%) moderate‐complexity lesions in the final 2 years of the study.
• ? The use of NSS increased from 28.6% of cases in 2005 to 60.0% of cases in 2009, which mirrored the increase in the proportion of operations performed for low‐complexity lesions (22.2% low‐complexity in 2005 to 70.6% in 2009, P < 0.01 for trend).

CONCLUSIONS

• ? The increasing use of NSS at our institution mirrored the increasing treatment of low‐complexity renal lesions.
• ? This may reflect an increased detection and referral of such lesions, or a shift towards treatment of lesions that in the past would have been under surveillance.
• ? Practice at our centre reflects a shifting paradigm towards preferential use of NSS for the treatment of suitable renal masses.

     

Robot-assisted partial nephrectomy for sporadic ipsilateral multifocal renal tumours

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Although laparoscopic excision of ipsllateral multifocal renal tumours is feasible, the average warm ischemia time is prolonged. Robotic partial nephrectomy in this subset of patients using blunt dissection to enucleate the tumour is feasible and safe. This study demonstrates further that robot‐assisted partial nephrectomy with a small margin of normal tissue is feasible and safe with an acceptable range of warm ischemia time in patients with sporadic ipsilateral multifocal renal tumours. This study also suggest that robotic partial nephrectomy for this particular group of patients may better preserve renal function compared to laparoscopic approach, however this needs to be confirmed with prospective comparative studies.

OBJECTIVE

? To report our short‐term results of robot‐assisted partial nephrectomy for treating sporadic multiple ipsilateral renal tumours.

METHODS

? Over a 3‐year period, eight patients with two or more ipsilateral renal masses underwent nine robotic partial nephrectomies in our institution. ? We evaluated the PADUA and R.E.N.A.L. nephrometry scores, intraoperative outcomes, histopathological characteristics, complications according to Clavien classification and renal function outcomes.

RESULTS

? In total, 19 tumours were removed from eight patients in nine procedures. Mean operative time was 199 ± 47 min (median 200; range 150–300). Mean size of the dominant lesion was 3.0 ± 1.1 cm (2.7; 1.6–4.8) and overall mean tumour size was 2.2 ± 1.2 cm (1.9; 0.4–4.8). Mean number of tumours removed per patient was 2.4. ? Median PADUA and R.E.N.A.L. scores were 7 and 6 (with the predominance of an anterior, non‐hilar position), respectively. ? Excluding the six off‐clamp resected tumours, the mean warm ischaemia time was 21 ± 9.2 min (21; 10–35). Mean estimated blood loss was 250 ± 154 mL (200; 100–500) and no patient required transfusion. There were no intraoperative complications or conversion to open surgery. One patient had atrial fibrillation, resolved with anti‐arrhythmic drugs. Mean length of stay was 4.2 ± 0.97 days. ? Sixteen of the nineteen tumours were malignant, most of papillary type and Fuhrman grade II. ? The mean decrease in glomerular filtration rate was 4%, with a mean follow‐up of 14 months.

CONCLUSIONS

? Robotic partial nephrectomy for sporadic ipsilateral multifocal renal tumours is feasible and safe. ? Off‐clamp resection of multiple tumours can also be safely performed in carefully selected lesions.