Single-Cell Chromatin and Gene-Regulatory Dynamics of Mouse Nephron Progenitors.

BACKGROUND: We reasoned that unraveling the dynamic changes in accessibility of genomic regulatory elements and gene expression at single-cell resolution will inform the basic mechanisms of nephrogenesis. METHODS: We performed single-cell ATAC-seq and RNA-seq both individually (singleomes; Six2GFP cells) and jointly in the same cells (multiomes; kidneys) to generate integrated chromatin and transcriptional maps in mouse embryonic and neonatal nephron progenitor cells. RESULTS: We demonstrate that singleomes and multiomes are comparable in assigning most cell states, identification of new cell type markers, and defining the transcription factors driving cell identity. However, multiomes are more precise in defining the progenitor population. Multiomes identified a "pioneer" bHLH/Fox motif signature in nephron progenitor cells. Moreover, we identified a subset of Fox factors exhibiting high chromatin activity in podocytes. One of these Fox factors, Foxp1, is important for nephrogenesis. Key nephrogenic factors are distinguished by strong correlation between linked gene regulatory elements and gene expression. CONCLUSION: Mapping the regulatory landscape at single-cell resolution informs the regulatory hierarchy of nephrogenesis. Paired single-cell epigenomes and transcriptomes of nephron progenitors should provide a foundation to understand prenatal programming, regeneration after injury, and ex vivo nephrogenesis.

Stem cells in Urology.

Stem cell research is rapidly expanding and has provided novel concepts in understanding and managing various diseases. Recent progress in translational and experimental urology has given insight about their utilization in the treatment and regeneration of urological structures. Chronic degenerative and neurological conditions affecting the lower urinary tract (LUT) are excellent targets for stem cell therapy. Their role has been particularly studied in bladder dysfunction, painful bladder syndrome, bladder outflow obstruction, stress urinary incontinence, erectile dysfunction, and urethral regeneration. However, the translation of this research in clinical domain is slow. Furthermore, regeneration of kidney using stem cells has been explored but remains challenging due to complexities of nephrons. Stem cells research in uro-oncology, especially bladder and prostate cancer, provided significant insight in understanding of pathogenesis processes and expanded potential therapeutic options. This review is centered to discuss application of stem cells and regenerative medicine in urology particularly human subject clinical studies and trials published in recent years.

Endoscopic Treatment for Large Multifocal Upper Tract Urothelial Carcinoma.

PURPOSE: We reviewed the oncologic and surgical outcomes of endoscopic treatments for low grade upper tract urothelial carcinoma, and assessed the prognostic significance of tumor size, location and multifocality. MATERIALS AND METHODS: We retrospectively reviewed all patients who underwent endoscopic treatment for low grade upper tract urothelial carcinoma at our institution between 2014 and 2019. Tumors were treated with a dual laser generator, which alternately produces holmium and neodymium lasers. A stringent ureteroscopic followup protocol was conducted. We looked for an association between outcome and tumor size, location or multifocality, and for predictive factors for time to local recurrence and progression. RESULTS: The cohort included 59 patients (62 renal units), 27% of tumors were multifocal and 40% were >2 cm. The median followup time was 22 months (IQR 11-41), and the median number of ureteroscopies was 5.5 (4-9). Local recurrence was observed in 46 renal units (74.1%) at a median of 6.5 months after initial surgery. Four patients (6.4%) developed disease progression and were referred for radical surgery: 2 had pathological progression and 2 had a rapid and high volume local recurrence, and 1 later developed metastatic disease. The progression-free rate was 93.2%. Tumor location in kidney (p=0.03, HR 1.95) and multifocality (p=0.005, HR 3.25) significantly predicted time to local recurrence. No factor predicted time to progression. CONCLUSIONS: Ureteroscopic treatment of large, multifocal, low grade upper tract urothelial carcinoma is feasible, does not involve significant complications and has good short-term oncologic outcomes, with a 93.2% progression-free survival rate. Tumors located in the kidney and multifocality yielded shorter time to local recurrence but not progression.

Stem cell-derived kidney organoids: engineering the vasculature.

Kidney organoids can be generated from human pluripotent stem cells (PSCs) using protocols that resemble the embryonic development of the kidney. The renal structures thus generated offer great potential for disease modeling, drug screening, and possibly future therapeutic application. At the same time, use of these PSC-derived organoids is hampered by lack of maturation and off-target differentiation. Here, we review the main protocols for the generation of kidney organoids from human-induced PSCs, discussing their advantages and limitations. In particular, we will focus on the vascularization of the kidney organoids, which appears to be one of the critical factors to achieve maturation and functionality of the organoids.

Factors Linked to Chronic Kidney Disease Among Stroke Survivors in Ghana.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor outcomes among stroke survivors. In Africa, where both stroke and CKD incidence rates are escalating, little, if anything, is known about the burden of CKD among stroke survivors. OBJECTIVE: To assess the frequency and factors associated with CKD among stroke survivors by primary stroke types. METHODS: Stroke registry data were prospectively collected on consecutively encountered stroke survivors seen at an out-patient clinic in Ghana between January 2018 and March 2020. We calculated estimated glomerular filtration rate (eGFR) using the CKD-EPI formula and defined CKD as eGFR <60ml/min. Factors associated with CKD were assessed using multiple logistic regression modelling. RESULTS: Among 759 stroke survivors, 159 had CKD giving a prevalence of 21.0% (95%CI: 18.1% - 23.8%). The mean age of those with CKD was 61.6 ± 14.2 years compared with 57.5 ± 13.6 years, p=0.0007 among those without CKD. Five factors remained significantly associated with CKD with the following adjusted odds ratio (aOR and 95% CI). Age per decile rise 1.30 (1.13-1.50), male sex 1.99 (1.36-2.93), rural dwelling residence 1.95 (1.06-3.59), prior use of antihypertensive meds before index stroke onset 1.63 (1.08-2.47), and number of antihypertensive medication classes 1.25 (1.06-1.45). CONCLUSION: 1 in 5 stroke survivors have evidence of chronic kidney disease in this Ghanaian study. Targeted interventions focusing on optimizing blood pressure control and rural dwellers may mitigate their risk for adverse outcomes.

Glomerular Morphology and Renal Function after Warm Ischemia by Main Artery or Selective Clamping in a Porcine Model.

OBJECTIVE: The study aimed to evaluate the ischemic and non-ischemic areas after selective arterial occlusion by using stereological analysis of glomeruli, and to compare them with main arterial clamping and sham-operated animals. MATERIALS AND METHODS: Twenty-four male pigs were used in the study. The animals were divided into 3 groups with 8 animals in each as follows: group sham, submitted to laparoscopic dissection of the renal pedicle but not submitted to ischemia; group arterial (A), submitted to left renal artery clamping; and group selective (S), submitted to left renal artery caudal branch occlusion. Groups A and S underwent 30 min of warm ischemia. Left and right kidneys were collected after 21 days and renal fragments were processed for stereological evaluation. Glomerular volume density (Vv[glom]), mean glomerular volume (MGV), and glomerular density were measured. Serum creatinine and urea were assessed preoperatively, 10 days after surgery, and before euthanasia. RESULTS: There was no significant difference among groups with regard to renal function. Renal weight and volume were similar among groups. Also, no difference was observed between the groups with regard to Vv[glom], MGV, and glomerular density, both when compared to its right control or when left kidneys were compared. CONCLUSIONS: Selective arterial clamping technique was neither superior nor inferior to main artery clamping.

Comparing Zero Ischemia Laparoscopic Radio Frequency Ablation Assisted Tumor Enucleation and Laparoscopic Partial Nephrectomy for Clinical T1a Renal Tumor: A Randomized Clinical Trial.

PURPOSE: We evaluated the functional outcome, safety and efficacy of zero ischemia laparoscopic radio frequency ablation assisted tumor enucleation compared with conventional laparoscopic partial nephrectomy. MATERIALS AND METHODS: A prospective randomized controlled trial was conducted from April 2013 to March 2015 in patients with cT1a renal tumor scheduled for laparoscopic nephron sparing surgery. All patients were followed for at least 12 months. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation group underwent tumor enucleation after radio frequency ablation without hilar clamping. The primary outcome was the change in glomerular filtration rate of the affected kidney by renal scintigraphy at 12 months. Secondary outcomes included changes in estimated glomerular filtration rate, estimated blood loss, operative time, hospital stay, postoperative complications and oncologic outcomes. The Pearson chi-square or Fisher exact, Student t-test and Wilcoxon rank sum tests were used. RESULTS: The trial ultimately enrolled 89 patients, of whom 44 were randomized to the laparoscopic radio frequency ablation assisted tumor enucleation group and 45 to the laparoscopic partial nephrectomy group. In the laparoscopic partial nephrectomy group 1 case was converted to radical nephrectomy. Compared with the laparoscopic partial nephrectomy group, patients in the laparoscopic radio frequency ablation assisted tumor enucleation group had a smaller decrease in glomerular filtration rate of the affected kidney at 3 months (10.2% vs 20.5%, p=0.001) and 12 months (7.6% vs 16.2%, p=0.002). Patients in the laparoscopic radio frequency ablation assisted tumor enucleation group had a shorter operative time (p=0.002), lower estimated blood loss (p <0.001) and a shorter hospital stay (p=0.029) but similar postoperative complications (p=1.000). There were no positive margins or local recurrence in this study. CONCLUSIONS: Zero ischemia laparoscopic radio frequency ablation assisted tumor enucleation enables tumor excision with better renal function preservation compared to conventional laparoscopic partial nephrectomy. Less blood loss and a shorter operative time were achieved with similar postoperative complication rates.

Development of hypertension is less frequent after bilateral nephron sparing surgery for bilateral Wilms tumor in a long-term survey.

PURPOSE: The option of nephron sparing surgery for unilateral Wilms tumor has been debated in the recent literature. This procedure is being used increasingly to preserve kidney tissue and function. However, nephron sparing surgery is feasible only for selected cases, and a higher local relapse rate has been observed. Moreover, a significant reduction of nephrons is associated with development of renal hypertension and progressive renal failure. We analyzed outcomes after bilateral partial nephrectomy and unilateral partial plus contralateral total nephrectomy in patients with bilateral Wilms tumor. MATERIALS AND METHODS: We analyzed data from the Society of Pediatric Oncology and Hematology database on 22 patients with bilateral Wilms tumor. Kidney size was measured using volumetric analysis of magnetic resonance imaging. Patients were matched with children who had undergone magnetic resonance imaging of the abdomen for other malignancies. RESULTS: Mean kidney volumes after unilateral partial plus total contralateral nephrectomy (66.9 cm(3)) were significantly greater than the reference kidneys (p = 0.028), whereas controls were equal to the bilateral partial nephrectomy group (49.7 cm(3), p = 0.959). Total kidney volume was significantly larger after bilateral partial nephrectomy (102.1 cm(3)) vs unilateral partial plus total contralateral nephrectomy (66.9 cm(3), p = 0.0338). Eight patients (66.7%) had renal hypertension after unilateral partial plus total contralateral nephrectomy but only 2 (20%) after bilateral partial nephrectomy (p = 0.043). Overall survival and relapse rates were equal between the groups and did not correlate with unfavorable histology. CONCLUSIONS: Our findings suggest that patients with bilateral Wilms tumor benefit from bilateral nephron sparing surgery. Hypertension is less common after bilateral partial nephrectomy, and rates of local relapse or disease associated death are distributed equally between the groups.

The Fate of Nephrons in Congenital Obstructive Nephropathy: Adult Recovery is Limited by Nephron Number Despite Early Release of Obstruction.

PURPOSE: Urinary tract obstruction and reduced nephron number often occur together as a result of maldevelopment of the kidneys and the urinary tract. We determined the role of nephron number on adaptation of the remaining nephrons of mice subjected to neonatal partial unilateral ureteral obstruction followed through adulthood. MATERIALS AND METHODS: Wild-type and Os/+ mice (the latter with 50% fewer nephrons) underwent sham operation or partial unilateral ureteral obstruction in the first 2 days of life. Additional mice underwent release of unilateral ureteral obstruction at 7 days. All kidneys were harvested at 3 weeks (weaning) or 6 weeks (adulthood). Glomerular number and area, glomerulotubular junction integrity, proximal tubular volume fraction and interstitial fibrosis were measured by histomorphometry. RESULTS: In the obstructed kidney unilateral ureteral obstruction caused additional nephron loss in Os/+ but not in wild-type mice. Glomerular growth from 3 to 6 weeks was impaired by ipsilateral obstruction and not preserved by release in wild-type or Os/+ mice. Proximal tubular growth was impaired and interstitial collagen was increased by ipsilateral obstruction in all mice. These conditions were attenuated by release of unilateral ureteral obstruction in wild-type mice but were not restored in Os/+ mice. Unilateral ureteral obstruction increased interstitial collagen in the contralateral kidney while release of obstruction enhanced tubular growth and reduced interstitial collagen. CONCLUSIONS: Unilateral ureteral obstruction in early postnatal development impairs adaptation to reduced nephron number and induces additional nephron loss despite release of obstruction. Premature and low birth weight infants with congenital obstructive nephropathy are likely at increased risk for progression of chronic kidney disease.

Modifying Dietary Sodium and Potassium Intake: An End to the 'Salt Wars'?

Excessive salt intake raises blood pressure, but the implications of this observation for human health have remained contentious. It has also been recognized for many years that potassium intake may mitigate the effects of salt intake on blood pressure and possibly on outcomes such as stroke. Recent large randomized intervention trials have provided strong support for the benefits of replacing salt (NaCl) with salt substitute (75% NaCl, 25% KCl) on hard outcomes, including stroke. During the same period of time, major advances have been made in understanding how the body senses and tastes salt, and how these sensations drive intake. Additionally, new insights into the complex interactions between systems that control sodium and potassium excretion by the kidneys, and the brain have highlighted the existence of a potassium switch in the kidney distal nephron. This switch seems to contribute importantly to the blood pressure-lowering effects of potassium intake. In recognition of these evolving data, the United States Food and Drug Administration is moving to permit potassium-containing salt substitutes in food manufacturing. Given that previous attempts to reduce salt consumption have not been successful, this new approach has a chance of improving health and ending the 'Salt Wars'.

NGAL is a Novel Target in Hypertension by Modulating the NCC-Mediated Renal Na Balance.

BACKGROUND: The expression of NGAL/lcn2 (neutrophil gelatinase-associated lipocalin) is directly modulated by mineralocorticoid receptor activation but its role in blood pressure control is unclear. METHODS: a potential relationship between NGAL plasma levels, systolic blood pressure and urinary Na excretion was assessed in the STANISLAS cohort. The specific role of NGAL/lcn2 in salt-sensitive hypertension was studied using lcn2-knockout mice (lcn2 KO) fed with low-Na diet (0Na). RESULTS: we show that NGAL plasma levels positively correlate with systolic blood pressure, whereas they negatively correlate with urinary Na excretion in subjects of the STANISLAS cohort. Prolonged feeding of lcn2 KO mice with a 0Na diet induced lower systolic blood pressure than that of the control group (wildtype), suggesting a role for NGAL/lcn2 in Na-balance homeostasis. Short-term or prolonged 0Na increased Na-Cl cotransporter (NCC) phosphorylation in the cortex of wildtype mice, which was prevented in lcn2 KO mice. Recombinant mouse lcn2 injections in lcn2 KO mice induced NCC phosphorylation in the kidney cortex, associated with decreased urinary Na excretion. Ex vivo experiments using kidney slices from lcn2 KO mice showed increased NCC phosphorylation by recombinant murine lcn2. In addition, recombinant murine lcn2 induced activation of CamK2ß (calcium/calmodulin-dependent protein kinase II ß subunit) phosphorylation in lcn2 KO mice and in kidney slices, providing an underlying mechanism involved in lcn2-induced NCC phosphorylation. Indeed, the inhibition of CamK2ß prevented NCC phosphorylation induced by recombinant lcn2 in kidney slices. CONCLUSIONS: we highlight a novel role of NGAL/lcn2 as a modulator of the activity of the renal sodium transporter NCC affecting salt-sensitive blood pressure.

[Mechanisms of action and clinical application of diuretics in intensive care medicine]. / Wirkmechanismen und klinische Anwendung von Diuretika in der Intensivmedizin.

The paired kidneys play a significant role in the human body due to the multitude of physiological tasks. Complex biochemical processes keep the sensitive electrolyte and water balance stable and thus ensure the organism's ability to adapt to exogenous and endogenous factors, which is essential for survival. The drug class of diuretics includes substances with very differing pharmacological characteristics. The functioning of the nephron is therefore indispensable for a deeper understanding of the pharmacodynamics, pharmacokinetics and side effect profile of diuretics. In the treatment of acute heart failure with pulmonary congestion, certain diuretics represent an important therapeutic option to counteract hypervolemia and thus an increase in preload. According to current data, diuretics have no proven benefits in the treatment or prevention of acute kidney injury but they can counteract hypervolemia and under certain conditions even reduce the use of renal replacement procedures.

[Methods for calculating the number of nephrons from ultrasound scans and kidney biopsies for nephrologists' use].

The interest in determining the number of nephrons in the kidney dates back to the 1960s, when an influential laboratory method for determining ex vivo the number of nephrons in the kidneys was described by Bricker. Over the years, various methods have been developed to estimate the number of nephrons in living beings as accurately as possible. These modern methods combine data such as the glomerular density, the percentage of glomeruli in sclerosis calculated from biopsy samples, and the kidney volume, which can be precisely estimated from magnetic resonance, CT scan, or specific ultrasound methods. As the reduction in the number of functioning nephrons is closely connected with an increased risk of progression of renal disease (especially in patients with nephrotic syndrome) and hypertension, its introduction into clinical practice could allow a precise stratification of progression risk in patients with kidney disease and a better understanding of the mechanisms that contribute to the loss of functioning nephrons.

Delineating and sparing functional nephrons for radiotherapy in the case of lymphoma with polycystic kidney disease.

PURPOSE: It is imperative to spare functioning kidneys from high radiation doses when they are near enough to radiotherapy (RT) target volumes in patients with polycystic kidney disease (PKD). To achieve this intent, we designed the unique approach that we report here. METHODS AND MATERIALS: The patient who has PKD, presented with B-cell lymphoma involving paraaortic lymph nodes. After completing chemotherapy, RT was planned to the residual nodal disease. The diagnostic positron emission tomography computed tomography (PETCT) scan was fused with the RT planning CT scan. 18F-2-deoxy-2(F)-fluro-d-glucose (FDG) avid active kidneys were contoured separately, and the treatment plan was optimized to avoid these volumes. RESULTS: The functional volume was 17.52% of the right kidney whereas it was 7.44% of the left. The mean doses were 4.61 Gy and 4.2 Gy, respectively. The baseline estimated glomerular filtration rate (eGFR) was >60 mL/min; at 18 months follow-up, it was 62 mL/min. CONCLUSIONS: Delineation of functional nephrons was feasible while utilizing the staging FDG-PETCT scan for radiotherapy contouring in our patient, which aided to achieve the optimal dose-volume constraints. Further studies are warranted to analyze and quantify the benefit of this easily accessible method in the future.

Epithelial Sodium Channel and Salt-Sensitive Hypertension.

The development of high blood pressure is influenced by genetic and environmental factors, with high salt intake being a known environmental contributor. Humans display a spectrum of sodium-sensitivity, with some individuals displaying a significant blood pressure rise in response to increased sodium intake while others experience almost no change. These differences are, in part, attributable to genetic variation in pathways involved in sodium handling and excretion. ENaC (epithelial sodium channel) is one of the key transporters responsible for the reabsorption of sodium in the distal nephron. This channel has an important role in the regulation of extracellular fluid volume and consequently blood pressure. Herein, we review the role of ENaC in the development of salt-sensitive hypertension, and present mechanistic insights into the regulation of ENaC activity and how it may accelerate sodium-induced damage and dysfunction. We discuss the traditional role of ENaC in renal sodium reabsorption and review work addressing ENaC expression and function in the brain, vasculature, and immune cells, and how this has expanded the implications for its role in the initiation and progression of salt-sensitive hypertension.

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

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.

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.

Directed Differentiation of Human Pluripotent Stem Cells for the Generation of High-Order Kidney Organoids.

Our understanding in the inherent properties of human pluripotent stem cells (hPSCs) have made possible the development of differentiation procedures to generate three-dimensional tissue-like cultures, so-called organoids. Here we detail a stepwise methodology to generate kidney organoids from hPSCs. This is achieved through direct differentiation of hPSCs in two-dimensional monolayer culture toward the posterior primitive streak fate, followed by induction of intermediate mesoderm-committed cells, which are further aggregated and cultured in three-dimensions to generate kidney organoids containing segmented nephron-like structures in a process that lasts 20 days. We also provide a concise description on how to assess renal commitment during the time course of kidney organoid generation. This includes the use of flow cytometry and immunocytochemistry analyses for the detection of specific renal differentiation markers.

Regulation of TFEB activity and its potential as a therapeutic target against kidney diseases.

The transcription factor EB (TFEB) regulates the expression of target genes bearing the Coordinated Lysosomal Expression and Regulation (CLEAR) motif, thereby modulating autophagy and lysosomal biogenesis. Furthermore, TFEB can bind to the promoter of autophagy-associated genes and induce the formation of autophagosomes, autophagosome-lysosome fusion, and lysosomal cargo degradation. An increasing number of studies have shown that TFEB stimulates the intracellular clearance of pathogenic factors by enhancing autophagy and lysosomal function in multiple kidney diseases, such as cystinosis, acute kidney injury, and diabetic nephropathy. Taken together, this highlights the importance of developing novel therapeutic strategies against kidney diseases based on TFEB regulation. In this review, we present an overview of the current data on TFEB and its implication in kidney disease.

High Salt Intake-Increased (Pro)renin Receptor Expression Is Exaggerated in the Kidney of Dahl Salt-Sensitive Rats.

The (P)RR ([pro]renin receptor) was identified as a new component of the renin-angiotensin system. We previously reported that high salt (HS) intake increased the (P)RR expression in several nephron segments of Sprague-Dawley rats. Other studies reported HS intake increased the XO (xanthine oxidase) activity and an MR (mineralocorticoid receptor) antagonist inhibited HS intake-increased (P)RR expression in the kidneys of Dahl salt-sensitive (DS) rats. The present study examined the effects of HS intake on (P)RR expression in the kidney of DS rats. Male DS rats were fed a normal salt diet or an HS diet for 4 weeks. Some of the rats fed on the HS diet were treated with the XO inhibitor, febuxostat, and the MR antagonist, spironolactone. Immunoblot and immunohistochemical analyses showed that HS intake increased (P)RR expression in the renal cortex by 22.6-fold, the proximal tubules by 4.9-fold and the distal tubules, respectively. Both febuxostat and spironolactone inhibited HS intake-increased (P)RR expression in the renal cortex. Febuxostat inhibited HS intake-increased (P)RR expression in the proximal tubules, whereas spironolactone inhibited HS intake-increased (P)RR expression in the distal tubules. Additionally, deoxycorticosterone acetate increased (P)RR expression in the renal cortex and distal tubules but not in the proximal tubules of DS rats fed the normal salt diet. These results indicate that HS intake greatly increases (P)RR expression in the renal cortex of DS rats. The mechanisms of HS intake-increased (P)RR expression may work in an XO-dependent manner in the proximal tubules and an MR-dependent manner in the distal tubules.

The Urinary and Osmoregulatory Systems of Birds.

The avian kidney contains both cortical or reptilian and medullary or mammalian nephrons. The kidney filters up to 11 times the total body water daily. Approximately 95% of this volume is reabsorbed by tubular reabsorption, which likely results from a change in the rate of filtration and/or the rate of reabsorption. These changes can result because of the antidiuretic hormone arginine vasotocin. The urinary concentrating ability generally varies inversely with body mass; however, birds can concentrate their urine, often at 2 to 3 times the osmolality of plasma. Further concentration of urine may occur by retroperistalsis.