Practical evaluation of the R.E.N.A.L. score system in 150 laparoscopic nephron sparing surgeries

ABSTRACT Introduction: Nephrometric scores play an interesting role in nephron sparring surgery (NSS) planning. The aim of this study is to evaluate if R.E.N.A.L. score (RS) is capable to predict the occurrence of adverse events in laparoscopic NSS. Materials and Methods: We prospectively studied 150 laparoscopic NSS between 2015 and 2018 to evaluate the relationship between RS and incidence of adverse events. Clavien 3 or superior complications, warm ischemia time (WIT) over 30 minutes, tumor violation, positive surgical margins (PSM) and necessity of amplification of renal parenchyma during the resection of the masses to obtain free margins were considered as adverse events. We compared each item of the RS isolated and divided the patients between low risk and high risk. Results: Adverse results occurred in 48 cases (32%). Amplification of the margin of resection was observed in 28 cases (19%). WIT exceeded 30 minutes in 9 cases (6.1%), complications Clavien 3 or superior occurred in 13 cases (9%) and PSM were detected en 6 cases (4%). Comparing the patients with adverse outcomes and each item of the RS we did not find any statistical difference, but when divided into high risk and low risk, we found that patients in the high risk group had a higher tendency to present ad-verse results - 25.84% vs. 44.26% (p=0.03). Conclusions: RS system is a good way to predict adverse outcomes in NSS, especially in cases over 7. Further studies should focus on robotic approach and patient's characteristics other than the masses' aspects.

Desarrollo renal fetal alterado y riesgo aumentado de enfermedades del adulto / Alterations in fetal kidney development and increased risk for adult diseases

El bajo peso al nacer (BP, < 2500 g), la restricción del crecimiento intrauterino (RCIU) y el parto prematuro (PP, < 37 semanas de gestación) son los factores clínicos más habituales para la programación alterada del número de nefronas y se asocian con un mayor riesgo de hipertensión, proteinuria y enfermedad renal futura en la vida. En la actualidad la evaluación indirecta del número total de nefronas mediante el uso de marcadores en el período posnatal representa el enfoque principal para evaluar el riesgo de evolución futura de los trastornos renales en los recién nacidos con BP, RCIU o PP.Se presentan los avances en la investigación en animales y sobre marcadores bioquímicos en humanos, y recomendaciones para la prevención del daño renal preconcepcional, incluidos los factores sociales y las enfermedades crónicas. La evidencia demuestra que la restricción de crecimiento y la prematuridad solas son capaces de modular la nefrogénesis y la función renal y, cuando son concurrentes, sus efectos tienden a ser acumulativos.

A low birth weight (LBW, < 2500 g), intrauterine growth restriction (IUGR), and preterm birth (PB, < 37 weeks of gestational age) are the most common clinical factors for an altered programming of nephron number and are associated with a greater risk for hypertension, proteinuria, and kidney disease later in life. At present, an indirect assessment of total nephron number based on postnatal markers is the most important approach to evaluate the risk for future kidney disorders in newborn infants with a LBW, IUGR or PB.Here we describe advances made in animal experiments and biochemical markers in humans, and the recommendations for the prevention of preconception kidney injury, including social factors and chronic diseases. According to the evidence, IUGR and prematurity alone can modulate nephrogenesis and kidney function, and, if occurring simultaneously, their effects tend to be cumulative.

Role of preoperative MR volumetry in patients with renal cell carcinoma for prediction of postoperative renal function after radical nephrectomy and nephron sparing surgery

ABSTRACT Purpose Preoperative computed tomography or magnetic resonance (MR) imaging are commonly used for radiological evaluation of renal cell carcinoma (RCC) before radical nephrectomy or nephron sparing surgery(NSS). This study aimed to assess the role of MRI for predicting postoperative renal function by preoperative estimation of renal parenchymal volume and correlation with glomerular filtration rate (GFR). Materials and Methods A prospective observational study was conducted from February 2015 to October 2016 at a tertiary care hospital in northern India. MR imaging was done on 3 Tesla MR scanner (Signa Hdxt General Electrics, Milwaukee, USA). MR volumetry was used to estimate the renal parenchymal volume. GFR was measured in all patients using Tc99m Diethyl-triamine-penta-acetic acid using Russell's algorithm. Such measurement was done preoperatively, and postoperatively 3 months after surgery. Results 30 patients with suspected RCC underwent NSS (n=10) and radical nephrectomy (n=20). Median tumour volume was 175.7cc (range: 4.8 to 631.8cc). The median volume of the residual parenchyma on the affected side was 84.25±41.97cc while that on the unaffected side was 112.25±26.35cc. There was good correlation among the unaffected kidney volume and postoperative GFR for the radical nephrectomy group (r=0.83) as well as unaffected kidney volume, total residual kidney volume and residual volume of affected kidney with postoperative GFR for the NSS group (r=0.71, r=0.73, r=0.79 respectively; P <0.05). Conclusion Preoperative residual parenchymal volume on MR renal volumetry correlates well with postoperative GFR in patients with RCC undergoing radical nephrectomy or NSS.

The aminoglycoside antibiotic gentamicin is able to alter metabolic activity and morphology of MDCK-C11 cells: a cell model of intercalated cells

It is well known that the aminoglycoside antibiotic gentamicin is capable of causing damage to kidney cells. Given the known involvement of Ca2+ in the nephrotoxic action of gentamicin, the purpose of this study was to establish a relationship between the concentration of intracellular Ca2+ ([Ca2+]i) and cellular cytotoxicity using MDCK-C11 cells, a clone that has several properties that resemble those of intercalated cells of the distal nephron. Changes in [Ca2+]i was determined using fluorescence microscopy. Cell viability was evaluated by the neutral red method, and cell cytotoxicity by the MTT method. The [Ca2+]i gradually increased when cells were exposed to 0.1 mM gentamicin for 10, 20, and 30 min. The presence of extracellular Ca2+ was found to be necessary to stimulate the increase in [Ca2+]i induced by gentamicin, since this stimulus disappeared by using 1.8 mM EGTA (a Ca2+ chelator). Morphological changes were observed with scanning electron microscopy in epithelial cells exposed to the antibiotic. Furthermore, with the MTT method, a decrease in metabolic activity induced by gentamicin was observed, which indicates a cytotoxic effect. In conclusion, gentamicin was able to alter [Ca2+]i, change the morphology of MDCK-C11 cells, and promote cytotoxicity.

Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of kidney damage: a review / Lipocalina associada à gelatinase neutrofílica (NGAL) como um biomarcador de lesão renal: uma revisão

Neutrophil gelatinase- associated lipocalin (NGAL) is a protein molecule predominantly expressed in the distal nephron after the occurrence of renal injury. Unlike the serum creatinine and the glomerular filtration rate, which are the renal function markers, the increased levels of NGAL, both in serum and urine, are closely linked to the structural injury to the nephron. Clinical studies indicate that a few hours after the occurrence of acute renal injury, the serum and urinary levels of NGAL are already significantly elevated, while the serum creatinine levels and renal clearance only undergo significant changes between 24-48h after injury. Thus, the use of renal function markers, usually assessed in the clinical practice, they may have some limitations also hindering the implementation of early measures aimed at protecting the kidneys. This literature review aims at examining the biological aspects and the applications of NGAL measurement in some clinical conditions, including kidney failure, kidney diseases and renal ischemia.

Lipocalina associada à gelatinase neutrofílica (NGAL) é uma molécula proteica predominantemente expressa na parte distal do néfron após a ocorrência de lesão renal. Diferentemente da creatinina sérica e da taxa de filtração glomerular, que são marcadores de função renal, os níveis aumentados de NGAL, tanto no soro quanto na urina, estão intimamente ligados a lesões estruturais do néfron. Os estudos clínicos indicam que poucas horas após a ocorrência da lesão renal aguda os níveis séricos e urinários de NGAL já se apresentam significativamente elevados, enquanto os níveis séricos de creatinina e a sua depuração renal apenas sofrem alterações significativas entre 24-48h após a lesão. Assim, a utilização de marcadores de função renal, usualmente avaliados na prática clínica, pode apresentar algumas limitações além de dificultar a aplicação de medidas precoces que visam a proteção renal. Esta revisão da literatura tem por objetivo analisar os aspectos biológicos e as aplicações da mensuração de NGAL em algumas condições clínicas, incluindo injúria renal, nefropatias e isquemia renal.

Effects of immunosuppression with tacrolimus and mycophenolate mofetil on renal histology and function in single kidney rats submitted to ischemia and reperfusion

PURPOSE: To evaluate renal histological changes and renal function in single kidney rats submitted to renal ischemia-reperfusion and to immunosuppression with tacrolimus and mycophenolate-mofetil. METHODS: Experimental study with 80 Wistar rats distributed into control, Sham and six other groups treated with immunosuppressive drugs. Animals undergoing surgery, right nephrectomy and left renal clamping, killed on the 14th day and analyzed for renal histology, urea and creatinine. RESULTS: The group receiving tacrolimus at higher doses (T3) showed renal histological lesions indicative of early nephrotoxicity, and significant increase in urea and creatinine. The group M (mycophenolate-mofetil alone) and the group M2 (mycophenolate-mofetil combined with half the usual dose of tacrolimus) presented a slight rise in serum urea. The groups using mycophenolate-mofetil alone or combined with tacrolimus showed creatinine levels similar to that of the group T3. CONCLUSIONS: Histologically, the association of injury by ischemia-reperfusion with the use of tacrolimus or mycophenolate-mofetil alone demonstrated a higher rate of renal changes typical of early nephrotoxicity. In laboratory, the combination of injury by ischemia-reperfusion with tacrolimus at higher doses proved to be nephrotoxic. .

Comparison of radiographic and pathologic sizes of renal tumors

Purpose The determination of the size of a renal tumor is important for staging, prognosis and selection of the appropriate surgical treatment. We investigated the difference of radiographic and pathologic size of renal tumors in a contemporary cohort of patients who underwent nephron sparing surgery and evaluated its clinical implications. Materials and Methods The records of 169 patients who received nephron sparing surgery for renal lesions suspicious for malignancy between January 2006 and December 2010 were reviewed retrospectively. Radiographic tumor size, defined as the largest diameter of tumor measured by CT images, and pathologic size, the largest diameter of tumor measured in the surgical specimen, were compared and analyzed. Results Among all subjects, mean radiographic and pathologic tumor size were 3.25 ± 1.78 cm and 3.03 ± 1.91 cm, respectively (P < 0.001), with a discrepancy of just 0.22 cm. When the patients were categorized according to radiographic tumor size in the 1 cm range, the mean radiographic tumor size was significantly greater than pathologic tumor size in the following groups: 2 to 3 cm (P < 0.001), 3 to 4 cm (P < 0.001), and 4 to 5 cm (P = 0.028). When radiographic and pathologic tumor sizes were compared according to the pathologic tumor subtype, a significant difference was observed only among those with clear cell renal carcinoma (P < 0.001). Conclusions Renal tumor size was overestimated by radiography as compared with pathology. The difference was just 0.22 cm with little clinical significance, suggesting that CT provides an accurate method to estimate renal tumor size preoperatively. .

Clampless laparoscopic partial nephrectomy: a step towards a harmless nephron-sparing surgery?

PURPOSE: To evaluate the results of our technique of clampless laparoscopic partial nephrectomy (LPN) and its impact as an emerging treatment for small renal masses (SMRs). MATERIALS AND METHODS: We reviewed our prospectively maintained database: data of 117 patients who consecutively underwent LPN at our Institution from January 2009 to December 2011 were studied. Patients were divided into 2 Groups based on operative technique: Group A: clampless-LPN (cl-LPN); Group B: conventional LPN (clamping of renal artery). Demographic and peri-operative data, complications, pre- and post-operative serum creatinine and estimated glomerular filtration rate (eGFR) were registered and compared by Student’s t- and Chi-square-tests (p-values < 0.05 considered statistically significant). RESULTS: 41 patients were in Group A and 76 in Group B. Groups were comparable in terms of preoperative data except for tumour’s size (2.35 ± 1.10 vs. 3.19 ± 1.57, Group A vs. B, respectively, p = 0.0029). Concerning perioperative data, warm ischemia time (WIT) was 0 min. in all Group A cases; mean WIT in Group B was 20.90 ± 9.27 min. One case (2.4%) in Group A (central tumour) was converted to conventional LPN. Mean eGFR postoperative decrease was higher in Group B (0.17 ± 9.30 vs. 4.38 ± 11.37 mL/min., A vs B, respectively, p = 0.0445). CONCLUSIONS: Notwithstanding the limits of the study, our results suggest that cl-LPN is a safe and effective technique, which allows surgeon to surgically treat SRMs even in case of complex location, without injuring kidney by ischemia.

Anatrophic nephrotomy as nephron-sparing approach for complete removal of intraparenchymal renal tumors

OBJECTIVE: Partial nephrectomy for small kidney tumors has increased in the last decades, and the approach to non-palpable endophytic tumors became a challenge, with larger chances of positive margins or complications. The aim of this study is to describe an alternative nephron-sparing approach for small endophytic kidney tumors through anatrophic nephrotomy. PATIENTS AND METHODS: A retrospective analysis of patients undergoing partial nephrectomy at our institution was performed and the subjects with endophytic tumors treated with anatrophic nephrotomy were identified. Patient demographics, perioperative outcomes and oncological results were evaluated. RESULTS: Among the partial nephrectomies performed for intraparenchymal tumors between 06/2006 and 06/2010, ten patients were submitted to anatrophic nephrotomy. The mean patient age was 42 yrs, and the mean tumor size was 2.3 cm. Mean warm ischemia time was 22.4 min and the histopathological analysis showed 80% of clear cell carcinomas. At a mean follow-up of 36 months, no significant creatinine changes or local or systemic recurrences were observed. CONCLUSION: The operative technique described is a safe and effective nephron-sparing option for complete removal of endophytic renal tumors.

Agenesia renal bilateral / Bilateral renal agenesia

Introducción. La agenesia renal bilateral es una anomalía congénita mortal rara, originada por la ausencia del desarrollo de las nefronas y fallo de la división del esbozo ureteral. Caso clínico. Paciente femenino de 25 años de edad con embarazo de 33 semanas 3 días de gestación referida para nuevos estudios de imagen por su médico tratante debido a sospecha de agenesia renal bilateral en su feto, en ultrasonido convencional. No había historia personal o familiar relevante. Se le practicó un ultrasonido obstétrico convencional y doppler color con reconstrucciones tridimensionales, demostrando en el feto, la ausencia de las arterias renales y riñones, con signo de la suprarrenal tumbada. Se observó, además agenesia vesical, mesocardia con dextroposición, tórax en campana con hipoplasia pulmonar y anhidramnios. Ocurrió óbito a las 35 semanas. Conclusión. Los hallazgos fueron congruentes con agenesia renal bilateral, con pronóstico fatal en el tercer trimestre del embarazo.

Secure reconstruction technique after partial nephrectomy irrespective of tumor size and location

Introduction: Nephron-sparing surgery for large renal masses is not considered a safe procedure because of high complication rate. We present our experience using expanded polytetrafluoroethylene (Gore-Tex®) and Hem-O-Lok® (Weck® Clip) as hemostatic agents during open partial nephrectomy (OPN) to perform nephron-sparing surgery for large renal masses. Materials and Methods: Sixty patients underwent OPN for suspicious renal cell carcinomas. Thirty-four patients with tumors < 2.5 cm in size underwent OPN with Gore-Tex® alone (group 1). Clinical data from a computerized database were reviewed and compared to a contemporary group of 26 patients with tumors ≥ 2.5 cm in size who underwent OPN with Gore-Tex® and Hem-O-Lok® (group 2). Results: The mean patient age was 53 years (range, 35-85 years), and the mean duration of follow-up was 41.8 months (range, 6-56 months). The mean cold ischemic times were 24.0 minutes (range, 12-37 minutes) and 35.3 minutes (range, 18-65 minutes) respectively in group 1 and 2. The tumor sizes in groups 1 and 2 were 1.7 ± 0.4 cm and 4.74 ± 2.75 cm, respectively. No major complications, such as urine leakage or delayed bleeding, were noted in either group. Conclusions: Nephron-sparing surgery using Gore-Tex® alone or a Gore-Tex® and Hem-O-Lok® combination was safe without high-priced hemostatic agents because the tensile strength was sufficient to maintain firmness in the repaired parenchyma. In addition, the procedure is easy to perform and takes less time to complete. Furthermore, major complications, recurrence, and impaired renal function did not occur with this procedure.

Utilización de los estudios de reserva funcional renal en pediatría / Role of renal functional reserve in pediatrics

Se midió la reserva funcional renal en 14 pacientes pediátricos. Estos niños mostraban pruebas de una disminución de la cantidad de nefronas debido al daño de las vías urinarias superiores o a la ausencia de un riñón. Los estudios se realizaron porque se consideró que corrían riesgo de hiperfiltración glomerular en ausencia de pruebas de insuficiencia renal crónica. Los pacientes presentaban electrolitos normales en suero, análisis de orina normal e índices de filtración glomerular mayores de 60 ml/min/1.73 m2. Siete estudios mostraron ausencia de hiperfiltración glomerular, dos confirmaron la hiperfiltración glomerular y uno arrojó un resultado ®dudoso¼ para hiperfiltración glomerular. El estudio fue poco satisfactorio desde el punto de vista técnico en cuatro casos, dos de los cuales fueron en niños con anomalías anatómicas macroscópicas. El informe muestra el uso de la reserva funcional renal en la evaluación de los niños en un centro nefrológico infantil.

MDCK cells express serotonin-regulable 11beta-hydroxysteroiddehydrogenase type 2

Prior to this work, we found that adrenal as well as extra-adrenal factors activate the response of renal 11beta-hydroxysteroid dehydrogenase 2 to stressful situations. These results -showing ways through which the organism hinders the pathological occupation of mineralocorticoid receptors by glucocorticoids leading to sodium retention and hypertension- prompted the present study on the nature of the above-mentioned extra-adrenal factors. Serotonin was chosen because of its properties as a widely distributed neurohormone, known to interact with glucocorticoids at many sites, also exhibiting increased levels and effects under stressful situations. We studied serotonin effects on 11beta-hydroxysteroiddehydrogenase 2 activity in a cell line derived from distal nephronpolarized-epithelium, employing 3H-corticosterone as substrate. The end-product, 3H- 11 -dehydrocorticosterone was separated from the substrate by HPLC and quantified. Serotonin stimulated 1I beta-hydroxysteroiddehydrogenase 2 activity only at 2nM and 25pM, the magnitude of the responsedepending also on substrate concentration. The stimulation was blocked by thespecific inhibitors methiothepin and ketanserin. We postulate that the organism partially prevents renal mineralocorticoid receptor occupancy by glucocorticoids, circulating at enhanced levels under stressful situations, through serotonin-mediated catabolic regulation of the 11beta-hydroxysteroid dehydrogenase 2 activity. Given many, mostly positive, interactions between both hormones, this might eventually pave the way to studies on a new regulatory axis.

Enfermedad e insuficiencia renal cronica: segunda parte / Disease and chronic renal failure: part two

La enfermedad renal cronica (ERC), se define como un proceso fisiopatológico de etiología múltiple, que produce pérdida progresiva e inexorable del numero funcional de nefronas, con la posibilidad de dar lugar a una condición denominada Insuficiencia Renal Cronica (IRC), la cual, a su vez, conduce al paciente a depender permanentemente de una terapia de reemplazo renal...

Chronic Kidney Disease, is defined as a pathophysiologic process with multiple etiologies, that produces a progressive and ineludible lost ofthe number of functional nephrones, with the possibility ofgiving place to a condition called Chronic Renal Failure, which itself drives the patient to permanent1y depend on Renal Replacement Therapy...

Effect of D-alpha-tocopherol on tubular nephron acidification by rats with induced diabetes mellitus

The objective of the present study was to determine if treatment of diabetic rats with D-alpha-tocopherol could prevent the changes in glomerular and tubular function commonly observed in this disease. Sixty male Wistar rats divided into four groups were studied: control (C), control treated with D-alpha-tocopherol (C + T), diabetic (D), and diabetic treated with D-alpha-tocopherol (D + T). Treatment with D-alpha-tocopherol (40 mg/kg every other day, ip) was started three days after diabetes induction with streptozotocin (60 mg/kg, ip). Renal function studies and microperfusion measurements were performed 30 days after diabetes induction and the kidneys were removed for morphometric analyses. Data are reported as means ± SEM. Glomerular filtration rate increased in D rats but decreased in D + T rats (C: 6.43 ± 0.21; D: 7.74 ± 0.45; D + T: 3.86 ± 0.18 ml min-1 kg-1). Alterations of tubular acidification observed in bicarbonate absorption flux (JHCO3) and in acidification half-time (t/2) in group D were reversed in group D + T (JHCO3, C: 2.30 ± 0.10; D: 3.28 ± 0.22; D + T: 1.87 ± 0.08 nmol cm-2 s-1; t/2, C: 4.75 ± 0.20; D: 3.52 ± 0.15; D + T: 5.92 ± 0.19 s). Glomerular area was significantly increased in D, while D + T rats exhibited values similar to C, suggesting that the vitamin prevented the hypertrophic effect of hyperglycemia (C: 8334.21 ± 112.05; D: 10,217.55 ± 100.66; D + T: 8478.21 ± 119.81æm²). These results suggest that D-alpha-tocopherol is able to protect rats, at least in part, from the harmful effects of diabetes on renal function.

Cambios en la presión sanguínea y en las concentraciones de electrolitos causados por falla renal en caninos / Changes in blood pressure and electrolitic concentrations due to renal failure in dogs

La falla renal aguda (FRA) y la falla renal crónica (FRC), en las cuales se afecta el 75 por ciento de las nefronas, son comunes en perros; los riñones no limpian la sangre de sustancias tóxicas, que se acumulan elevando los niveles de Nitrógeno Ureico Sanguíneo (BUN) y la creatinina, que al ser medidas en el laboratorio, sirven para dar el diagnostico de la falla; además se genera un desbalance electrolítico por la incapacidad del riñón de reabsorber o secretar iones. La presión sistólica y diastólica, que pueden ser detectadas, como en el presente estudio, mediante una manga de presión pediátrica colocada sobre la arteria humeral, aumento especialmente en el FRC. Todo esto lleva a cambios en el corazón y por tanto a cambios del electrocardiograma (ECG)...