Roles and regulation of bone morphogenetic protein-7 in kidney development and diseases

The gene encoding bone morphogenetic protein-7(BMP7) is expressed in the developing kidney in embryos and also in the mature organ in adults. During kidney development, expression of BMP7 is essential to determine the final number of nephrons in and proper size of the organ. The secreted BMP7 acts on the nephron progenitor cells to exert its dual functions: To maintain and expand the progenitor population and to provide them with competence to respond to differentiation cues, each relying on distinct signaling pathways. Intriguingly, in the adult organ, BMP7 has been implicated in protection against and regeneration from injury. Exogenous administration of recombinant BMP7 to animal models of kidney diseases has shown promising effects in counteracting inflammation, apoptosis and fibrosis evoked upon injury. Although the expression pattern of BMP7 has been well described, the mechanisms by which it is regulated have remained elusive and the processes by which the secretion sites of BMP7 impinge upon its functions in kidney development and diseases have not yet been assessed. Understanding the regulatory mechanisms will pave the way towards gaining better insight into the roles of BMP7, and to achieving desired control of the gene expression as a therapeutic strategy for kidney diseases.

Insights into kidney stem cell development and regeneration using zebrafish

Kidney disease is an escalating global health problem,for which the formulation of therapeutic approaches using stem cells has received increasing research attention.The complexity of kidney anatomy and function,which includes the diversity of renal cell types,poses formidable challenges in the identification of methods to generate replacement structures.Recent work using the zebrafish has revealed their high capacity to regenerate the integral working units of the kidney,known as nephrons,following acute injury.Here,we discuss these findings and explore the ways that zebrafish can be further utilized to gain a deeper molecular appreciation of renal stem cell biology,which may uncover important clues for regenerative medicine.

Synchronous bilateral multiple chromophobe cell renal carcinoma complicated with right kidney cyst: a case report

Synchronous bilateral multiple chromophobe cell renal carcinoma is rare; here we report a case diagnosed with bilateral renal multiple tumors complicated with a cyst in the right kidney. Retroperitoneal laparoscopic bilateral nephron sparing surgery was performed and there was no serious postoperative renal dysfunction. Pathological and immunohistochemical diagnoses of both tumors were chromophobe cell renal carcinoma. The patient has been doing well without any evidence of recurrence or metastasis for 6 months.

Ultrasound-guided Open Nephron Sparing Surgery without Renal Artery Occlusion for Central Renal Tumors

From January 2008 to January 2013, 11 patients with central renal tumors underwent ultrasound-guided open nephron sparing surgery（ONSS） without renal artery occlusion. We removed the lesions, and the cut edges of the tumors were negative. Thus, we deduced that ultrasound-guided ONSS is suitable for the cases with obscure tumor boundary or multiple lesions. It could achieve the purpose of thoroughly removing lesions, as well as to expand the application range of nephron sparing surgery.

Renal progenitors: Roles in kidney disease and regeneration

Kidney disease is a devastating condition that affects millions of people worldwide, and its prevalence predicted to significantly increase. The kidney is complex organ encompassing many diverse cell type organized in a elaborate tissue architecture, makin regeneration a challenging feat. In recent years, there ha been a surge in the field of stem cell research to develo regenerative therapies for various organ systems. Here we review some recent progressions in characterizing th role of renal progenitors in development, regeneration and kidney disease in mammals. We also discuss how the zebrafish provides a unique experimental anima model that can provide a greater molecular and genet understanding of renal progenitors, which may contribut to the development of potential regenerative therapies fo human renal afflictions.

Transumbilical laparoendoscopic single-site surgery(LESS) partial nephrectomy:a median follow-up of 2 years

Objective:Nephron-sparing surgery(NSS) for small renal masses offers a similar functional and oncological outcome to that of radical surgery.Laparoendoscopic single-site surgery(LESS) emerges as an advanced alternative for reduced invasiveness and improves cosmesis;LESS is developing quickly and its indications have been expanded,but still in its infancy.The aim of this paper is to report our preliminary experience in transumbilical LESS partial nephrectomy(LESS-PN),so as to assess its utility, safety and efficacy.Methods:From August 2009 to October 2010,3 patients underwent transumbilical LESS-PN via a novel multi-channel TriPort by a single experienced urologist in our institution.Patient demographics,perioperative and follow-up data were prospectively collected and analyzed.Results:All the three procedures were successfully completed.A 5-mm ancillary trocar was utilized in all 3 cases.The mean operative duration was 226.3(210-254 min) with an estimated blood loss of 56.7 ml (20-100 ml).Mean warm ischemia time was 35.7 min(19-48 min).One patient was transfused due to postoperative bleeding. The recovery was uneventful and mean length of postoperative stay was 13 days(12-14 days).At the latest follow-up,all patients remained symptom-free and had normal renal function without evidence of recurrence,and they were delighted for a hidden transumbilical scar.Conclusion:Transumbilical LESS-PN is a feasible and safe procedure albeit extremely technically challenging.Surgical outcomes at a median follow-up of 2 years are promising,while currently it should be reserved for highly selected patients with favorable tumor anatomy and performed by a very experienced laparoscopic surgeon.

Evaluation of nephron sparing surgery for renal tumors:a single institution experience

Objective:The aim of the study was to report the experience of National Cancer Institute(NCI),Cairo University,Egypt,in managing various benign and malignant renal tumors with nephron sparing surgery(NSS),and to assess its safety and feasibility.Methods:Reviewing the literature for NSS,and records of patients who underwent NSS in the period from January 2000 to December 2009 at National Cancer Institute,Cairo University regarding the patient and tumor related characteristics,the indication for NSS,operative technique,postoperative complications,full histopathological data,and follow up results.Results:The total number of patients was 17.Mean age at surgery was 30.7 years(range 1.5-65 years).Five patients had bilateral tumors during surgery.The mean tumor size was 4.5 cm(range 1-9 cm).All patients had normal preoperative kidney functions.Seven patients had an absolute indication for NSS,6 patients had a relative indication,and 4 patients had an elective indication.All the 5 patients with bilateral tumors underwent bilateral simultaneous surgery.Cold ischemia was used in 8 patients,1 patient was exposed to warm ischemia,manual compression was used in 2 patients,and no vascular control was applied in 6 patients.Complications were encountered in 2 patients,one of them had urinary leakage which needed reoperation,and the other had subcutaneous hematoma which was treated conservatively.Histopathological analysis revealed Wilm's tumor(8 patients),angiomyolipoma(4 patients),renal cell carcinoma(4 patients),and hydatid cyst(1 patient).All patients had negative surgical margin.For patients with Wilm's tumor,the mean follow up was 21.4 months(range 0-94 months),2 patients had local recurrence,and 1 patient had distant metastasis.For patients with RCC,the mean follow up was 15.3 months(5-33 months),no patients had local recurrence or distant metastasis.All patients had normal kidney functions during postoperative and follow up periods.Conclusion:NSS is a feasible safe procedure that can be done with acceptable complications rate and it provides a good solution for patients with bilateral tumors,early localized renal cell carcinoma,and benign tumors.

Assessment of Warm and Cold Ischemia on Functions of the Operated Kidney with ^99mTc-DMSA in Renal Masses: A Prospective and Randomized Study

Objective: To examine the effect of warm and cold ischemia on functions of the operated kidney in cases with a normal contralateral kidney undergoing nephron sparing surgery. Methods: This study enrolled 40 patients with a normal contralateral kidney and without a renal function threatening risk factor, who were operated with NSS. The patients were randomized at admission. They were divided into 2 equal groups as warm and cold ischemia. An ice application for 10 minutes was done to cold ischemia group after clamping renal artery. Renal functions were evaluated with Technesium-99m-Dimercaptosuccinic Acid (DMSA) and serum creatinine at the preoperative and postoperative (day 1, day 15, month 6, and month 12) period. Statistical analysis was done with Mann Whitney U test, Wilcoxon Signed Rank test, and Fredman test. A p value below 0.05 was considered statistically significant. Results: There were no significant differences between the groups in terms of age, body mass index, ischemia time, tumor size, amount of hemorrhage, and procedure time. Both groups had a significantly higher DMSA uptake at the preoperative period compared with the postoperative period (postoperative day 1, day 15, month 6, and month 12) (p 0.001). However, both groups had similar DMSA uptake results at the postoperative period. Preoperative and postoperative creatinine levels were not significantly different from each other in both groups. Conclusion: Based on tumor localization, nephron sparing surgery without use of superficial cooling appears as a viable option for small renal masses.

Single-site laparoscopic partial nephrectomy: Where are we going?

AIM:To review an evolution of laparoscopic surgery,there has been a growing interest in laparoendoscopic single-site surgery(LESS).METHODS:A comprehensive electronic literature search was conducted using PubM ed database to identify all publications relating to LESS-partial nephrectomy(PN).The research includes articles published from April 2008 to January 2014.We focused our attention only on articles in which were cited the single-site surgical technique(laparoscopic and robotic),tumour stage and grade,mean tumour size,intraoperative variables,blood loss and transfusion rate,length of postoperative stay and complication rates,Clavien classification,positive of surgical margins,pain assessment at discharge.RESULTS:A total of 9 studies were collected with 221patients included.The mean patients age was 62 years.The mean tumor size was 2.35 cm with a mean operative time of 181 min(range 111-270 min)and 58.3%were done by robot.The mean ischemia time was 23.6min.The 25.8%of patients underwent an unclamp LESS-PN.Mean estimated blood loss was 296 mL and median length of hospital stay was 4 d.The rate of severe post-operative complications(≥Clavien gradeⅢ)was 5.4%.Not all surgical series of LESS-PN or Robotic-LESS-PN shows conversion in Multiport Laparoscopic or Open Surgery.Regarding oncologic outcomes,surgical margins were positive 4%of patients(9/221),no distant or port-site metastases were recorded.CONCLUSION:LESS-PN and RLESS-PN are feasible and associated with reduced postoperative pain,shorter median hospital stay,shorter recovery time,and better cosmetic satisfaction without compromising surgical and oncological safety.

Nephrolithiasis: Insights into Biomimics, Pathogenesis, and Pharmacology

Background:In the last decade,a varied prevalence of lifestyle-mediated health ailments ranging from infectious disorders to non-curable diseases has been observed.Globally the stone formation(lithiasis)in human kidneys has increased the trauma and economic burden.Furthermore,affordable rapid diagnosis,clinical trials,and therapeutics have to be addressed with newer holistic approaches.Objective:The current comprehensive review attempts to study kidney stones using emerging translational,con-ventional,and non-conventional research models,which include prokaryotic and eukaryotic systems(in vitro,semi-in vivo,and in vivo).Methods:The study eligibility criteria included systematic reviews and meta-analyses to explore various lithiatic models.Further,PubMed,PubMed Central,CINAHL Plus,Scopus,Web of Science,and EMBASE were used as data sources for the current study.A Measurement Tool to Assess Systematic Reviews(AMSTAR)was used.Results:All curated literature from past 55 years(1967-2022)were considered for this review with keywords as"Experimental models for human kidney stones"AND"Nephrolithasis"AND"Urolithasis".A total of 765 abstracts were reviewed for inclusion with 414 selected for full-text review.A total of 47 studies were analyzed.Mean AMSTAR score of 6.96/11(±1.84)suggests moderate quality of the systematic reviews.Conclusion:This review will empower clinicians,veterinarians,and researchers for a better understanding of the pathogenesis,causative factors,and prevalence of nephrolithiasis and urolithiasis and their associated mech-anisms with rapid,reliable,and reproducible models.The findings of the study will aid in designing global healthcare policy and regional insurance for lithiatic disorders with effective therapeutics which will result in an increased quality of life,leading to better health and hygiene.

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.

Effects of Cyclosporine A on the Development of Metanephros in the Pregnant BALB/c Mice

Background：Cyclosporine A （CsA） is a commonly used clinical immunosuppressant.However,CsA exposure in rabbits during the gestation period was shown to cause a postnatal decrease in the number of nephrons,with the effects remaining unknown.In this study,we aimed to explore the effects of CsA on metanephros development in the pregnant BALB/c mice.Methods：Pregnant mice were randomly divided into two groups,and CsA （10 mg·kg^-1·d^-1） was subcutaneously injected from gestation day 10.5 to day 16.5 in the CsA group,whereas a comparable volume of normal saline was given to the control group.All of the mice were sacrificed on gestation day 17.5 and serum CsA concentration was measured.The fetuses were removed and weighed,and their kidneys were prepared for histological assessment and polymerase chain reaction assay.In an in vitro experiment,embryo kidneys of fetal mice on gestation day 12.5 were used,and CsA （10 tmol/L） was added in the culture of the CsA group.The growth pattern of the ureteric bud and nephrons was assessed by lectin staining.Results：No significant differences in the weight of embryo （4.54 ± 1.22 vs.3.26 ± 1.09 mg） were observed between the CsA and control groups,the thickness of the cortical （510.0 ± 30.3 vs.350.0 ± 29.7 μm,P 〈 0.05） and nephrogenic zone （272.5 ± 17.2 vs.173.3 ± 24.0 μm,P 〈 0.05）,and the number of glomeruli （36.5 ± 0.7 vs.27.5 ± 2.1,P 〈 0.05） were reduced in the CsA group when compared to the control group.The cell proliferation of Ki-67 positive index between control and CsA group （307.0 ± 20.0 vs.219.0 ± 25.0,P 〈 0.05） in the nephrogenic zone was decreased with the increase of apoptotic cells （1 7.0 ± 2.0 vs.159.0 ± 33.0,P 〈 0.05）.The mRNA expression of WT-1,Pax2,and Pax8 was downregulated by CsA treatment.As for the in vitro CsA group,the branch number of the ureteric bud was decreased in the CsA-treated group with the nephrons missing in contrast to control after the incubation for 24 h and 72 h （all P〈 0.0001）.Conclusion：Treatment of CsA suppressed metanephros development in the pregnant mice;however,the potential action of mechanism needs to be further investigated.

Management of solid renal tumour associated with von Hippel-Lindau disease

Von Hippel-Lindau （VHL） disease is a rare autosomal dominant disorder caused by germ line mutations of the VHL tumour suppressor gene. it predisposes affected individuals to develop a variety of neoplasms, including haemangioblastomas of the central nervous system, retinal angiomas, renal cell carcinomas （RCCs）, pheochromocytomas and cysts of the kidneys and epididymis. Germ line VHL mutations have been found in all VHL disease families. RCC occurs in 25% to 45% of patients with VHL disease and is one of the leading causes of death.

Clinical Observation on Chemical Damage of Nephron and the Preventive and Therapeutic Effects of Baoshen Mixture (保肾合剂) on It

Objective： To observe the change of nephron damaged by chemotherapy and to evaluate the effect of Baoshen Mixture （保肾合剂, BSM） in protecting and treating damaged nephrons. Methods： Four hundred tumor patients with normal renal function and ready to receive chemotherapy were randomly assigned to two groups. Both groups received one cycle of chemotherapy program of 28-30 days with conventional hydratization, alkalization and chloridization. To the 200 cases in the treated group BSM was given orally thrice a day, 150 mL every time for 15 successive days and the other 200 cases in the control group were treated by chemotherapy alone. The clinical efficacy was compared after treatment, and the changed condition of damaged nephrons were monitored dynamically and compared at different time points （the 3rd, 7th, 14th and 21st day after chemotherapy） by measuring the micro-globulin 132 （13 2-MG）, albumin （AIb） and immunoglobulin G （IgG） levels in urine with radioimmunoassay （RIA）. Results： （1） The effective rates in the treated group at the 4 time points of observation were all higher than those in the control group respectively （P〈0.05 or P〈0.01）; （2） Less occurrence of abnormal 132-M, AIb and IgG levels on the 14th and 21st day in the treated group took place compared to that in the control group （P〈0.01）; （3） Urinary levels of 13 2-MG, AIb and IgG reached the peak on the 7th day in both groups, and then, they came down gradually and returned to the normal level on the 21 st day. However, comparison between the two groups showed that all the three parameters in the treated group on day 3, 14 and 21 were lower than the respective one at the corresponding time points in the control group （P〈0.05 or P〈0.01）. Conclusion： The chemotherapy damage on nephron is regular in time, and reversible when treated suitably. TCM shows a marked effect in protecting and treating the damage on nephron caused by chemotherapy.