Kidney Mass Research Articles

Efek Minuman Keras Oplosan terhadap Perubahan Histopatologi Organ Renal Tikus Wistar Jantan


 Mixed liquor is a liquor mixed with other substances, mainly ethanol and methanol. Mixed liquor can cause kidney destruction. The aim of this study was to investigate the effect of mixed liquor toward kidney's microscopic and macroscopically changes. This study used 24 rats which were divided into 4 groups consist of 1 control group and 3 experimental groups. The first, second, and third experimental groups were given ethanol 1,296ml/2 days; methanol 0,2592ml/2days and aquades 1,4448ml/2 days for 5 days; 11 days and 17 days, respectively. Afterward rats were terminated and the right kidney mass was measured. The kidney tissue was prepared for histological examination and the number of necrotic cell was calculated. According to Kruskal Wallis test, kidney mass was not significantly different (p>α) while total necrotic cells was significantly different (p<α). This study showed that rats induced with mixed liquor for 5 , 11, and 17 days resulted in kidney microscopically change.

Melanotic Xp11 translocation renal cancer: a report of a distinctive case and a review of the literature

BackgroundMelanotic Xp11 translocation renal cancer (TRC) is a newly described exceedingly rare tumor, and its characterization remains controversial. This study aimed to describe a case of distinctive melanotic Xp11 TRC and to elucidate its clinicopathological and molecular genetic features.Case presentationA 44-year-old Chinese female presented with a left renal mass. Abdominal ultrasonography and computed tomography (CT) scans revealed a 4.5 cm × 4.0 cm mass in the left kidney. Grossly, the well-demarcated mass was black with moderately firm consistency. Microscopic examination indicated that the tumor was characterized by the presence of nests and cords of polygonal cells with clear and granular eosinophilic cytoplasm, central round to oval nuclei and occasional nucleoli. Intracytoplasmic melanin was observed in approximately 45% of tumor cells. Uniquely, the tumor presented with intranuclear eosinophilic pseudoinclusions and thick-walled stromal blood vessels. IHC showed that tumor cells were diffusely positive for TFE3 and exhibited patchy and weak HMB45 staining. FISH confirmed the presence of TFE3 rearrangement.ConclusionThis case is the twentieth published case of melanotic Xp11 TRC. Moreover, the present patient had a favorable prognosis given that she was disease free at her 113-month postoperative follow-up. Our case adds to the small body of literature on these exceptionally rare tumors and widens their clinicopathological spectrum.

Arterial stiffness is associated with visceral fat mass in kidney transplanted patients—A nationwide cohort study

Arterial stiffness, visceral fat, and hyperglycemia are acknowledged risk factors for adverse outcomes after transplantation, but whether arterial stiffness is associated with visceral adipose tissue and hyperglycemia is unknown. We studied 162 non-diabetic kidney transplant recipients 8-10weeks after transplantation. Arterial stiffness was measured as pulse wave velocity (PWV) by SphygmoCor and visceral fat using a validated software applied on DXA scans. Also a standard oral glucose tolerance test was performed. Median PWV was 8.6m/s (IQR 7.3-10.4m/s). Patients in the upper quartile of PWV had 31%-106% higher visceral fat percentage (P<0.001), they were older (P<0.001) and had a fasting plasma glucose of 5.8mmol/L that was higher than in the other quartiles (P=0.006). In univariate analysis, visceral fat percentage and age were the parameters strongest associated with PWV (P<0.001), but cholesterol and glucose were also significant (P<0.05). In multivariate analysis, visceral fat was the only significant predictor of PWV along with age (P<0.001). In conclusion, arterial stiffness is significantly associated with visceral fat but not hyperglycemia in non-diabetic kidney transplant patients. We identified age and VAT as risk variables for arterial stiffness. A potential reversibility of arterial wall stiffness with reduction in VAT needs further study.

Sunitinib rechallenge with dose escalation in progressive metastatic renal cell carcinoma: A case report and literature review.

Rationale:We aimed to present a case of sunitinib rechallenge with dosage escalation after disease progression, hopefully, providing an optional approach to the personalized medication management of progressive metastatic renal cell carcinoma (mRCC).Patient concerns:The patient was admitted to hospital due to right kidney mass, with merged enlargement of retroperitoneal lymph nodes. Subsequent surgery and sunitinib treatment was administered.Diagnoses:Postoperative pathologic diagnosis was type II papillary renal cell carcinoma (pRCC) (Fuhrman grade 3) with metastases of retroperitoneal lymph nodes (T1aN1M0).Interventions:The patient underwent cytoreductive nephrectomy followed by treatment of sunitinib standard therapy (4/2 schedule) and alternative schedules according to different disease status. The patient received alternative 2/1 schedule while experiencing grade 3/4 adverse events. Re-challenge with sunitinib upon disease progression and metastasectomy were given. After second disease progression, sunitinib rechallenge with dose escalation was administered. Around 2/1 schedule showed desirable efficacy and better tolerance.Outcomes:After 4 months of sunitinib individualized treatment, a complete response with retroperitoneal metastases was achieved. Rechallenge with sunitinib after disease progression and also rechallenge with dose escalation after second disease progression were effective.Lessons:Cessation of sunitinib in patients with complete response is not suggested. Also, strategy of subsequently administered sunitinib after metastasectomy is seemed to be effective. What is more, sunitinib rechallenge with escalation to 62.5 mg probably possess value in progressive mRCC and has a well tolerance when sunitinib is rechallenged. Based on this case, we probe a feasible alternative strategy in personalized therapy of sunitinib, hoping for providing referable insights into the detailed strategies of individual treatment for patients with mRCC.

GIANT CLEAR CELL RENAL CARCINOMA: A CASE REPORT

Objective: This article is aimed to report an unusual presentation of renal cancer T4N0M0 in which the tumor weighed about 5 kilograms in a patient admitted to Urology Department of Hasan Sadikin Hospital in Bandung, Indonesia, in August 2016. Case presentation: We report a case 62 year old male with history of growing mass in his left abdominal. There are also painless hematuria and weight loss of approximately 10 kg over the past 2 years. Discussion: Physical examination found a significant palpable, immobile and mild tender mass in the left upper quadrant of the abdomen. Abdominal Pelvic Computed Tomography (CT) scan revealed inhomogenous hypodens mass in the left kidney. Resection of the tumor revealed a 5 kg (22 x 25 x 18 cm, with total volume of 9.900 cm3) encapsulated neoplasm. Histophatological examination revealed a clear cell type renal cell carcinoma (RCC) with positive margin and Fuhrmann grade 2. In Asia, a giant chromophobe RCC exceeding 10 kg in weight was reported in 2009. As for previously reported giant clear cell RCC, we found out the data to be very limited. Conclusion: Giant RCC is rare, especially clear cell type in histophatological result. The size of the tumor reported in this article is considered as the largest-sized giant clear cell RCC ever reported in Asia. The size of the tumor in this case presented several challenges in the operative settings. However, the outcome and six months post-operative follow-up of the patient was satisfying in which there was no presence of single symptom within the six-month follow-up period.

The Probability of Aggressive Versus Indolent Histology Based on Renal Tumor Size: Implications for Surveillance and Treatment

BackgroundWhile the probability of malignant versus benign histology based on renal tumor size has been described, this alone does not sufficiently inform decision-making in the modern era since indolent malignant tumors can be managed with active surveillance. ObjectiveTo characterize the probability of aggressive versus indolent histology based on radiographic tumor size. Design, setting, and participantsWe evaluated patients who underwent radical or partial nephrectomy at Mayo Clinic for a pT1-2, pNx/0, M0 solid renal tumor between 1990 and 2010. Pathology was reviewed by one genitourinary pathologist. High-grade clear-cell renal cell carcinoma (RCC), high-grade papillary RCC, collecting duct RCC, translocation-associated RCC, hereditary leiomyomatosis RCC, unclassified RCC, and malignant non-RCC tumors were all considered aggressive, as well as any tumors demonstrating coagulative necrosis (except low-grade papillary RCC) or sarcomatoid differentiation. The remaining benign and malignant tumors were considered indolent. Outcome measurements and statistical analysisCancer-specific survival (CSS) was estimated using the Kaplan-Meier method. Logistic regression models were used to estimate the probability of malignant and aggressive histology based on tumor size. Sex-stratified analyses were also performed. Results and limitationsOf the 2650 patients included, there were 1860 patients with indolent tumors (300 benign; 1560 malignant) and 790 with aggressive tumors. The 10-yr CSS was 96% for indolent malignant tumors and 81% for aggressive malignant tumors. The predicted percentages of any malignant histology as well as aggressive histology increased with tumor size. Specifically, 2cm, 3cm, and 4cm tumors have an estimated 84%, 87%, and 88% likelihood of malignancy, respectively, and an 18%, 24%, and 29% likelihood of aggressive histology, respectively. For any given tumor size, men had a greater chance of aggressive histology than women. Potential limitations of this observational surgical cohort include selection bias. ConclusionsWe present tumor size-based estimates of the probability of aggressive histology for renal masses. This information should be useful for initial patient counseling and management. Patient summaryActive surveillance is an option for kidney masses, even if they are malignant. Beyond knowing whether the mass is benign or cancer, it is important to know whether or not it is an aggressive tumor. This study presents tumor size-specific and sex-specific estimates of the probability of cancer overall and aggressive cancer among patients with a kidney mass in order to aid with initial decision-making.

Acquired von Willebrand Disease Secondary to Clear Cell Renal Cell Carcinoma.

Background: Acquired von Willebrand disease (AvWD) is a rare and often underdiagnosed disease that typically is associated with lymphoproliferative, cardiovascular disease, and myeloproliferative disease. It is challenging to diagnose as it requires a hemostatic challenge to present itself.Case Presentation: This is a 46-year-old male with a history of multiple sclerosis complicated by neurogenic bladder who presented with intermittent gross painless hematuria. He underwent a gross hematuria workup. Cystoscopy demonstrated active bleeding from the right ureteral orifice. CT Urogram showed a filling defect in the right renal pelvis and endophytic 3 cm solid, enhancing left kidney mass. The patient underwent diagnostic cystourethroscopy, bilateral retrograde pyelogram demonstrating no filling defects bilaterally. Right ureteropyeloscopy demonstrated diffuse patchy erythema of the infrarenal collecting system with biopsies obtained. His postoperative course was complicated by gross hematuria requiring cystoscopy which demonstrated no upper tract bleeding and small pulsatile bleeding vessel in the bladder requiring cauterization. Hematology was consulted to rule out bleeding diathesis with workup demonstrating a von Willebrand deficiency (vWD). He had no family history of vWD and an AvWD was suspected. Hematologic workup was consistent with AvWD, type 2B vWD also known as a platelet-type von Willebrand disease. Renal pelvis biopsies were negative for pathology. Further investigation of the left renal mass confirmed a biopsy-proven clear cell renal cell carcinoma (ccRCC). He underwent a laparoscopic left radical nephrectomy with final pathology demonstrating pT1 ccRCC with negative margins. Postoperatively his repeat laboratories demonstrated normal factor VIII activity, ristocetin cofactor, and vWF antigen with normalized activated partial thromboplastin time. Follow-up imaging demonstrated no further evidence of disease supporting the hypothesis of a paraneoplastic syndrome from his ccRCC that caused an AvWD.Conclusion: This is the first case report to our knowledge of a paraneoplastic AvWD secondary to ccRCC. This should be on your differential when there is abnormal bleeding in the setting of renal masses.

Polypoid Endometriosis Presenting as a Renal Cortical Tumor

A 41-year-old female patient presented with left-sided flank pain and gross hematuria temporally unrelated to her menstrual cycle. Abdominal computed tomography scan showed a large left-sided solid, enhancing kidney mass radiographically consistent with renal cell carcinoma. Following surgical resection, histopathological examination revealed polypoid endometriosis. Polypoid endometriosis is rare and mimics a neoplasm clinically, radiographically, and on gross examination. Patients with polypoid endometriosis often present with symptoms related to mass effect rather than classic endometriosis hallmark symptoms such as dyspareunia, dysmenorrhea, and cyclic abdominal pain. Treatment includes surgical resection.

The effect of kidney volume estimation on dosimetry in lutetium-177 DOTATATE therapy.

The kidneys are the dose-limiting organ in lutetium-177 DOTATATE therapy. Therefore, it is advisable to perform critical organ dosimetry focussed on renal dose in treated patients. A key uncertainty in such dose estimates is the use of standard phantoms to represent the individual patient. The primary aim of this study was to investigate the accuracy of methods for estimating kidney size, and hence absorbed kidney dose, by comparison with individual measurements from computed tomography (CT) imaging. Kidney volume was measured using diagnostic CT images for 57 patients who underwent lutetium-177 DOTATATE therapy. Kidney mass was also estimated in two ways: using the standard adult phantoms, as well as through the application of a weight scaling factor to these phantoms and their organs. Dose calculations were performed for each of the three methods using OLINDA/EXM software. Scaling of the phantom by patient weight gave a more accurate result when compared with the CT gold standard than the standard phantom. The dose difference from the CT method had mean values of 1.4% (SD=22.6%) and 8.4% (SD=21.5%) for scaled and unscaled, respectively. Patient weight was not found to be a good predictor of kidney mass in these patients (r of 0.12 from linear regression analysis). The most accurate method of organ volume estimation would be individual measurements from CT imaging; however, where this is not possible, scaling of organ masses by weight ratio is more accurate than the use of the standard phantom.

Two in One: Epithelioid angiomyolipoma within a classic kidney angiomyolipoma - a case report

BackgroundEpithelioid angiomyolipoma is defined as potentially malignant mesenchymal neoplasm, characterized by proliferating epithelioid cells, whereas classic angiomyolipoma, composed of fat, smooth muscle cells and dysmorphic vessels, is defined as a potentially benign. The usual or classic angiomyolipoma is often found incidentally on imaging studies, relatively easily identified due to the presence of fat, in contrast to the epithelioid angiomyolipoma that can pose diagnostic challenges.Case presentationWe report a 51-year-old female patient in which an ultrasonography examination showed a solid mass close to the right renal pelvis with hypoechoic and hyperechoic areas. A differential diagnosis of atypical sinus lipomatosis, lipoma and a transitional cell carcinoma was postulated whereas in a subsequent computed tomography a classic angiomyolipoma was postulated. A re-examination by contrast enhanced ultrasound revealed a striking perfusion difference of the hypoechoic and hyperechoic areas. The hypoechoic area showed homogenous and prolonged enhancement whereas the hypoechoic area displayed a marked slower contrast material flooding and a relatively rapid wash out. The histological analysis from the biopsy of the hyperechoic area showed a classic angiomyolipoma, whereas the sample of the hypoechoic central portion revealed an epithelioid angiomyolipoma. A nephrectomy was performed because of the malignant potential of the epithelioid variant of the angiomyolipoma.ConclusionsA solid kidney mass with two sharply defined parts, one-part compatible with a classical angiomyolipoma and the other being suspected of carcinoma, is rare, but also illustrative and instructive. The combination of different imaging modalities in the work up of a solid renal mass facilitated to discriminate benign from malignant areas.

Effect of captivity on morphology: negligible changes in external morphology mask significant changes in internal morphology.

Captive breeding programmes are increasingly relied upon for threatened species management. Changes in morphology can occur in captivity, often with unknown consequences for reintroductions. Few studies have examined the morphological changes that occur in captive animals compared with wild animals. Further, the effect of multiple generations being maintained in captivity, and the potential effects of captivity on sexual dimorphism remain poorly understood. We compared external and internal morphology of captive and wild animals using house mouse (Mus musculus) as a model species. In addition, we looked at morphology across two captive generations, and compared morphology between sexes. We found no statistically significant differences in external morphology, but after one generation in captivity there was evidence for a shift in the internal morphology of captive-reared mice; captive-reared mice (two generations bred) had lighter combined kidney and spleen masses compared with wild-caught mice. Sexual dimorphism was maintained in captivity. Our findings demonstrate that captive breeding can alter internal morphology. Given that these morphological changes may impact organismal functioning and viability following release, further investigation is warranted. If the morphological change is shown to be maladaptive, these changes would have significant implications for captive-source populations that are used for reintroduction, including reduced survivorship.

MitoQ supplementation prevent long-term impact of maternal smoking on renal development, oxidative stress and mitochondrial density in male mice offspring

To investigate the effect of maternal MitoQ treatment on renal disorders caused by maternal cigarette smoke exposure (SE). We have demonstrated that maternal SE during pregnancy increases the risk of developing chronic kidney disease (CKD) in adult offspring. Mitochondrial oxidative damage contributes to the adverse effects of maternal smoking on renal disorders. MitoQ is a mitochondria-targeted antioxidant that has been shown to protect against oxidative damage-related pathologies in many diseases. Female Balb/c mice (8 weeks) were divided into Sham (exposed to air), SE (exposed to cigarette smoke) and SEMQ (exposed to cigarette smoke with MitoQ supplemented from mating) groups. Kidneys from the mothers were collected when the pups weaned and those from the offspring were collected at 13 weeks. Maternal MitoQ supplementation during gestation and lactation significantly reversed the adverse impact of maternal SE on offspring’s body weight, kidney mass and renal pathology. MitoQ administration also significantly reversed the impact of SE on the renal cellular mitochondrial density and renal total reactive oxygen species in both the mothers and their offspring in adulthood. Our results suggested that MitoQ supplementation can mitigate the adverse impact of maternal SE on offspring’s renal pathology, renal oxidative stress and mitochondrial density in mice offspring.

Management of the Incidental Kidney Mass in the Nephrology Clinic.

The most common urologic malignancy seen in the nephrology clinic is clear cell renal cell carcinoma (RCC), which is generally asymptomatic and often found incidentally during imaging. Greater than 25% of patients with RCC have concomitant CKD at diagnosis, presumably because of overlapping risk

Active Surveillance for Localized Renal Masses: Tumor Growth, Delayed Intervention Rates, and >5-yr Clinical Outcomes

BackgroundActive surveillance (AS) has gained acceptance as a management strategy for localized renal masses. ObjectiveTo review our large single-center experience with AS. Design, setting, and participantsFrom 2000 to 2016, we identified 457 patients with 544 lesions managed with AS from our prospectively maintained kidney cancer database. A subset analysis was performed for patients with ≥5-yr follow-up without delayed intervention (DI). Outcome measurements and statistical analysisLinear growth rates (LGRs) were estimated using linear regression for the initial LGR (iLGR) AS interval and the entire AS period. Overall survival (OS) and cumulative incidence of DI were estimated with Kaplan-Meier methods utilizing iLGR groups, adjusting for covariates. DI was evaluated for association with OS in Cox models. Results and limitationsMedian follow-up was 67 mo (interquartile range [IQR] 41–94 mo) for surviving patients. Cumulative incidence of DI (n=153) after 1, 2, 3, 4, and 5 yr was 9%, 22%, 29%, 35%, and 42%, respectively. Median initial maximum tumor dimension was 2.1cm (IQR 1.5–3.1cm). Median iLGR and overall LGR were 1.9 (IQR 0–7) and 1.9 (IQR 0.3–4.2) mm/yr, respectively. Compared with the no growth group, low iLGR (hazard ratio [HR] 1.25, 95% cumulative incidence [CI] 0.82–1.91), moderate iLGR (HR 2.1, 95% CI 1.31–3.36), and high iLGR (HR 1.87, 95% CI 1.23–2.84) were associated with DI (p=0.003). The iLGR was not associated with OS (p=0.8). DI was not associated with OS (HR 1.34, 95% CI 0.79–2.29, p=0.3). Five-year cancer-specific mortality (CSM) was 1.2% (95% CI 0.4–2.8%). Of 99 patients on AS without DI for >5 yr, one patient metastasized. ConclusionsAt >5 yr, AS±DI is a successful strategy in carefully managed patients. DI often occurs in the first 2–3 yr, becoming less likely over time. Rare metastasis and low CSM rates should reassure physicians that AS is safe in the intermediate to long term. Patient summaryIn this report, we looked at the outcomes of patients with kidney masses who elected to enroll in active surveillance rather than immediate surgery. We found that patients who need surgery are often identified early and those who remain on active surveillance become less likely to need surgery over time. We concluded that active surveillance with or without delayed surgery is a safe practice and that, when properly managed and followed, patients are unlikely to metastasize or die from kidney cancer.

Allometric and Biphasic Allometric Growth of Major Organs in Hatchling Female Alligators (Alligator mississippiensis)

Allometric equations represent relationships between a morphological size (e.g., organ size) or physiological rate (e.g., metabolic rate) and body mass using the equation Y=aMb, where Y is morphological size or physiological rate, a is elevation or y‐intercept, b is slope and M is animal body mass. Vertebrate organ growth relative to body mass varies between allometric (b&lt;1.0 or b&gt;1.0) and isometric (b=1.0), depending on the organ and species. In mammals and reptiles, heart and lungs have been shown to grow isometrically, whereas in mammals, the kidneys and liver have been shown to grow with negative allometry. Most allometric studies of organ growth focus on changes that span orders of magnitude achieved between juvenile and adult life stages or between various species of widely divergent size. This may ignore or possibly ‘wash out’ trends that occur during rapid growth in very early life stages. Large avian species and reptiles grow most rapidly during their early life history, and there can be significant genetic or ‘clutch’ effects for reptiles with different parentage. Large crocodilians, like the American alligator, can increase in size by a factor of &gt;10 during their first year post‐hatching and show physiological differences between clutches that persist at least through the first year post‐hatching. We measured organ growth in hatchling female alligators from 5 clutches at 8–10 time points during their first order of magnitude of growth (~45 g to ~500 g). We tracked each individual alligator (N&gt;90) from their original egg identity (clutch and egg mass). Animals were anesthetized and sacrificed, and their organs carefully dissected. Organ and animal wet masses (±0.1 mg and ±0.1 g, respectively) were measured upon sacrifice, and dry masses were measured after organs and the animal's carcass had fully dried (2d ‐ several weeks at 70°C) so that mass did not change by &gt;1% between &gt;18‐h spaced measurements. Slopes and intercepts for regressions of organ mass against body mass were compared among clutches using ANCOVA. Breakpoint analyses determined the intersection with minimum residual sum of squares or the intersection where the differences of the residual variances were smallest. Preliminary data showed that dry kidney and liver size increased in relative proportion to body mass (b~1.0), and heart size (b~0.9) and lung size (b~0.75) decreased in relative proportion. Dry masses showed less variation compared to wet masses. Within the first order of magnitude of growth, breakpoint analyses revealed that kidney and liver mass grew more quickly during the hatchlings first weeks‐to‐months post‐hatching, and our study is the first to document biphasic organ growth in hatchlings of a large, long‐lived reptile. Hatchling alligators appear to undergo a very early period of rapid kidney and liver growth following hatching, and these two organs grow with different kinetics than lung or heart tissue. Reasons for this disparity will be an area of further research.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Metabolic acidosis inhibits AMPK function in kidney cells

The metabolic sensor AMP‐activated protein kinase (AMPK) is stimulated by cellular metabolic depletion. We have shown that AMPK activation inhibits kidney membrane transport proteins. AMPK‐activated processes protect kidney cells from further metabolic depletion and damage. AMPK is tightly regulated, and its pharmacological activation can protect kidneys from superimposed injury, such as acute kidney injury (AKI). Conversely, AMPK is inhibited in chronic kidney disease (CKD). Therefore, pharmacologic AMPK activators are proposed as therapies to slow CKD progression. However, the mechanisms by which AMPK may promote kidney survival are unclear. CKD results in metabolic acidosis (MA) due to the inability of kidneys to excrete non‐volatile acid. MA, if untreated, has severe health sequelae such as worsening of kidney function. We hypothesized that there is cross‐talk between acid‐base status and AMPK signaling, and that dysregulation of AMPK function by MA disrupts kidney regeneration in the setting of CKD. We used kidney epithelial cell lines in culture and adult male C57BL/6 mice (WT) and AMPKβ1‐KO mice for our experiments. Cells were exposed to media at either pH 7.3–7.4 (control) or 6.9–7.0 (acidic) for 3 d ± an AMPK activator (last 16 h). We found that, as compared to cells grown at pH 7.4, kidney cells grown in acidic media have reduced baseline AMPK activity and blunted pharmacologic AMPK activation. We then evaluated changes in AMPK function in WT mice fed a normal diet vs. WT mice given 1.5% saccharin ± 0.28 M NH4Cl in drinking water for 2 mo. To evaluate the AMPK pathway in kidney tissue, we examined levels of phosphorylation of acetyl CoA carboxylase (pACC) by immunoblot. Mice on the acidogenic diet developed MA without significant weight loss compared to mice on the control diet (blood pH 7.2 vs 7.3 ± 0.01). In mice after UNX, the superimposed MA induced a statistically significant decrease in pACC, compared to mice with UNX on a control diet. We also evaluated differences in BUN in WT vs. AMPKβ1‐KO mice 3 mos. after sham surgery or UNX, a model for reduced kidney mass. Both WT and KO mice post‐UNX had significant worsening of kidney function (higher BUN) compared to sham‐operated mice of the same genotype. However, we did not observe any significant differences in BUN between WT and KO mice following sham or UNX. Our results point to worsening in kidney function post‐UNX and to a direct inhibition of the AMPK pathway in the setting of reduced kidney mass and MA. This AMPK inhibition may be detrimental to kidney regeneration in these settings.Support or Funding InformationKeck School of Medicine of USC; USC/UKRO Kidney Research CenterThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Body Mass‐Specific Na, K‐ATPase Activity in the Medullary Thick Ascending Limb – Implications for Species‐Dependent Urine Concentrating Mechanisms

In general, the mammalian whole body mass‐specific metabolic rate correlates positively with maximal urine concentration (Umax), irrespective of whether or not the species have adapted to arid or mesic habitat. Accordingly, we hypothesized that the thick ascending limb (TAL) of a rodent with markedly higher whole body mass‐specific metabolism than rat exhibits a substantially higher TAL metabolic rate as estimated by Na, K‐ATPase activity and Na, K‐ATPase α1 gene and protein expression. The kangaroo rat inner stripe of the outer medulla exhibits significantly higher mean Na, K‐ATPase activity (~70%) compared to two rat strains (Sprague‐Dawley and Munich‐Wistar), extending prior studies showing rat activity exceeds rabbit. Furthermore, higher expression of Na, K‐ATPase α1 protein (~4–6‐fold) and mRNA (~13‐fold) and higher TAL mitochondrial volume density (~20%) were seen in the kangaroo rat compared to both rat strains. Rat TAL Na, K‐ATPase α1 protein expression is relatively unaffected by body hydration status or, as shown previously, by dietary Na, arguing against confounding effects from two unavoidably dissimilar diets: grain‐based diet without water (kangaroo rat) or grain‐based diet with water (rat). We conclude that higher TAL Na, K‐ATPase activity contributes to relationships between whole body mass‐specific metabolic rate and high Umax. With the combination of 70% greater Na, K‐ATPase activity and 50% greater total kidney mass:body mass ratio for the kangaroo rat compared to the rat, and assuming all other factors remain equal, the contribution of TAL Na, K‐ATPase activity to overall whole body metabolism would be about 2.5‐fold greater in the kangaroo rat compared to the rat. More vigorous TAL Na, K‐ATPase activity in the kangaroo rat than in the rat may contribute to its steeper Na and urea axial concentration gradients, adding support to a revised model of the urine concentrating mechanism, which hypothesizes a leading role for vigorous active transport of NaCl, rather than countercurrent multiplication, in generating the outer medullary axial osmotic gradient.Support or Funding InformationNIDDK DK083338 (TP) and DK110621 (TR), NSF IOS‐0952885 (TP), Joint DMS/NIGMS‐NSF DMS‐1263943 (TP), APS/NSF Fellowships (MA).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Three‐dimensional analysis of potassium deprivation‐induced tubular remodeling using optical clearing

Tubular remodeling can be induced by various stimuli and plays a critical role in functional adaptation. For instance, hypokalemia is associated with increased kidney mass caused by cellular hypertrophy and hyperplasia. However, accurate quantitative analysis of tubular remodeling is still lacking since most kidney morphometry was performed with two‐dimensional techniques. Here, we combined optical clearing and advanced light microscopy as a new approach for three‐dimensional analysis of tubular remodeling in mouse kidneys, upon dietary potassium (K+) restriction.Adult C57BL/6J mice were fed for 3 days with K+‐deficient diet (approx. 0.002% K+) or normal K+ diet (1.2% K+) and were injected with Bromodeoxyuridine (BrdU) intraperitoneally before kidneys were perfusion‐fixed 4 h later. Kidneys were cut into 1.0–1.5 mm thick slices and stained for BrdU then optically cleared with Ethyl Cinnamate. Confocal microscopy was used to identify the total number of BrdU positive cells per unit volume. In addition, 4 μm sections were used for co‐staining of BrdU with segment‐specific antibodies to localize proliferating cells. Whole blood was collected via terminal cardiac puncture and analyzed using i‐STAT analyzer (Abbot Point of Care Inc.).As expected, serum K+ levels were significantly lower in mice on K+ ‐deficient diet than in mice on normal diet (3.7 ± 0.1 mmol/L vs. 4.2 ± 0.1 mmol/L, p&lt;0.005, n=6–7). After optical clearing, confocal microscopy allowed high‐resolution imaging of BrdU positive cells within the whole thick kidney slice. Quantification of BrdU positive cells revealed that the cell proliferation rate was low in control mice, but that K+ restriction strongly induced cell proliferation (3748 ± 392 cells/mm3 vs. 1089 ± 341 cells/mm3 p&lt;0.05, n=3). Co‐localization using thin sections and segment‐specific markers revealed that this increase in proliferation was restricted to the S3 segment of the proximal tubule and outer medullary collecting duct intercalated cells.In this study, we validated a combination of optical clearing and advanced light microscopy as a new toolbox for imaging and quantification of tubular remodeling, which will decrease our reliance on biased two‐dimensional morphometric techniques and time‐consuming stereological approaches. Our analysis revealed that dietary K+ restriction caused preferential hyperplasia in S3 segments and in intercalated cells. The former observation might reflect a functional adaptation after low‐K+ induced injury of proximal tubules, whereas the latter likely represent a compensatory response to increase renal potassium uptake.Support or Funding InformationDFG German Research Foundation Fellowship (332853055) and Else Kröner‐Fresenius Stiftung (2015_A197) to TS, Humboldt Foundation and National Health and Medical Research Council of Australia Research Fellowships to VGP, R01DK098141 to JAM, and R01DK054983 to DHE.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Long-term exercise restores hydrogen sulfide in the kidney and contributes to exercise benefits in 5/6 nephrectomized rats

ABSTRACTPhysical exercise is shown to have protective effects on chronic kidney disease (CKD). CKD itself is associated with a reduction in renal hydrogen sulfide (H2S) concentration. This study was designed to investigate whether protective effects of exercise in 5/6 nephrectomized (5/6 NX) rats is associated with H2S levels in the kidney? Twenty four male Wistar rats weighing 250–300 g were assigned into 4 groups: 1- Sham 2- Sham exercise 3–5/6 NX 4–5/6 NX+exercise. To induce CKD, 4 days after removing upper and lower one-third parts of the left kidney, total right nephrectomy was performed. In the Sham groups, anesthesia and surgery were performed like the other groups without removal of the kidney mass. Exercise was performed by treadmill at a speed of 18 m/min for 8 weeks. At the end of the twelfth week, blood and kidney samples were collected to measure renal function (levels of plasma urea and creatinine), oxidative stress markers (renal MDA level and SOD activity), and histological indices. Eight weeks exercise significantly improved serum creatinine, BUN, renal MDA level, SOD activity, renal sympathetic nerve activity (RSNA), hypertension, and renal histology in addition to renal H2S level compared to the 5/6 NX group. The results suggest that regular exercise improves renal oxidative status and ameliorates renal damage, hypertension, and RSNA in 5/6 nephrectomized rats. These improvements by exercise might be associated with the increase in renal H2S level.

Molecular targeted therapies of renal cell carcinoma considering life stage of the patient: Two case reports.

Molecular targeted therapies have markedly improved the prognosis of metastatic renal cell carcinoma (RCC) and patients are able to receive specific treatments depending on their condition. The cases of two patients who presented with large RCC with very different statuses were examined in the current study. One of the patients was elderly with numerous comorbidities, and the other was young and had Case 1 was an elderly female with various comorbidities including a history of cerebral infarction and impaired eyesight. A 7 cm solid mass in the left kidney, pulmonary metastases and a shrunken right kidney were identified. Conservative treatment was selected and the patient underwent treatment with oral sorafenib for 5 years without experiencing disease progression. Case 2 was a middle-aged male in a good general condition who had a 19 cm left renal mass and multiple metastases. Due to the tumor size, the patient was initially treated with oral pazopanib to reduce the renal tumor volume and was able to undergo left radical nephrectomy after 6 months. Molecular targeted therapies were thus used to treat these patients taking into account each patient's life stage; case 1 was treated without surgery for six years and case 2 received treatment as a neoadjuvant.