Renal Medicine

Author(s):  
William White

The kidney causes problems for medical students and junior doctors alike— the convoluted journey from plasma to urine, the conundrum of what is reabsorbed and excreted where, and the tangled web of the glomerulonephritides are traditionally learnt, rather than actually understood. As in all clinical medicine, a good place to start is with the fundamen­tals of the organ in question. Passage from plasma to urine follows the pathway: ● Blood ● Glomerulus ● Tubules ● Collecting duct ● Ureter ● Bladder ● Urethra. The primary functions of the kidney are: ● Removal of toxins ● Electrolyte homeostasis ● Maintenance of acid– base balance ● Activation of vitamin D ● Stimulation of erythropoiesis ● Maintenance of blood volume. The challenge then is to implement these basics by being sensitive to deviations from normal physiology: recognizing the accumulation of any potential toxins (hyperkalaemia, uraemia, and acidosis) or the lack of any synthetic products (hypocalcaemia and anaemia), suggesting triggers for such deviations, and pinpointing the specific parts of the anatomy that may be malfunctioning in some way so as to cause impairment. Despite its bad reputation, the kidney reveals more about itself than any other organ and, in theory, should be the easiest to monitor. It achieves this through its raison d’être: urine. Its presence, absence, con­tents, smell, and colour offer a running commentary on the activity of the renal tract at any given point in time— it is the internal, intangible work­ings of specialized cells made physical, measurable, and dippable. So, far from being those much- feared Objective Structured Clinical Examination (OSCE) stations, the dipstick and the catheter are our friends. Or they should be, for it is our ability to harness the information that they pro­vide, allied to the series of numbers on the oft- requested ‘U&Es’ (urea and electrolytes), against a background of wide- ranging symptoms that will make us sensitive to the running of the kidney. This— not just our ability to regurgitate the three types of renal tubular acidosis— is what is at stake in this chapter.

2000 ◽  
Vol 279 (3) ◽  
pp. F459-F467 ◽  
Author(s):  
Gheun-Ho Kim ◽  
Stephen W. Martin ◽  
Patricia Fernández-Llama ◽  
Shyama Masilamani ◽  
Randall K. Packer ◽  
...  

Increased systemic acid intake is associated with an increase in apical Na/H exchange in the renal proximal tubule mediated by the type 3 Na/H exchanger (NHE3). Because NHE3 mediates both proton secretion and Na absorption, increased NHE3 activity could inappropriately perturb Na balance unless there are compensatory changes in Na handling. In this study, we use semiquantitative immunoblotting of rat kidneys to investigate whether acid loading is associated with compensatory decreases in the abundance of renal tubule Na transporters other than NHE3. Long-term (i.e., 7-day) acid loading with NH4Cl produced large decreases in the abundances of the thiazide-sensitive Na-Cl cotransporter (TSC/NCC) of the distal convoluted tubule and both the β- and γ-subunits of the amiloride-sensitive epithelial Na channel (ENaC) of the collecting duct. In addition, the renal cortical abundance of the proximal type 2 Na-dependent phosphate transporter (NaPi-2) was markedly decreased. In contrast, abundances of the bumetanide-sensitive Na-K-2Cl cotransporter of the thick ascending limb and the α-subunit of ENaC were unchanged. A similar profile of changes was seen with short-term (16-h) acid loading. Long-term (7-day) base loading with NaHCO3resulted in the opposite pattern of response with marked increases in the abundances of the β- and γ-subunits of ENaC and NaPi-2. These adaptations may play critical roles in the maintenance in Na balance when changes in acid-base balance occur.


Author(s):  
Gertrude Arthur ◽  
Jeffrey L. Osborn ◽  
Frederique B. Yiannikouris

Prorenin receptor (PRR), a 350-amino acid receptor initially thought of as a receptor for the binding of renin and prorenin has been shown to be multifunctional. In addition to its role in the renin angiotensin system (RAS), PRR also transduces several intracellular signaling molecules and is a component of the vacuolar H+-ATPase that participates in autophagy. PRR is found in the kidney and particularly in great abundance in the cortical collecting duct. In the kidney, PRR participates in water and salt balance, acid-base balance, autophagy and plays a role in development and progression of hypertension, diabetic retinopathy, and kidney fibrosis. This review highlights the role of PRR in the development and function of the kidney namely the macula densa, podocyte, proximal and distal convoluted tubule and the principal cells of the collecting duct and focuses on PRR function in body fluid volume homeostasis, blood pressure regulation and acid-base balance. This review also explores new advances in the molecular mechanism involving PRR in normal renal health and pathophysiological states.


1998 ◽  
Vol 274 (3) ◽  
pp. F596-F601 ◽  
Author(s):  
Géza Fejes-Tóth ◽  
Erzsébet Rusvai ◽  
Emily S. Cleaveland ◽  
Anikó Náray-Fejes-Tóth

AE2 mRNA and protein is expressed in several nephron segments, one of which is the cortical collecting duct (CCD). However, the distribution of AE2 among the different cell types of the CCD and the function of AE2 in the kidney are not known. The purpose of this study was to determine the distribution of AE2 mRNA among the three CCD cell types and to examine the effects of changes in acid/base balance on its expression. Following NH4Cl (acid) or NaHCO3 (base) loading of rabbits for ∼18 h, CCD cells were isolated by immunodissection. AE2 mRNA levels were determined by RT-PCR and were normalized for β-actin levels. We found that CCD cells express high levels of AE2 mRNA (∼500 copies/cell). AE2 mRNA levels were significantly higher in CCD cells originating from base-loaded than acid-loaded rabbits, with an average increase of 3.7 ± 1.07-fold. The effect of pH on AE2 mRNA levels was also tested directly using primary cultures of CCD cells. CCD cells incubated in acidic media expressed significantly lower levels of AE2 mRNA than those in normal or alkaline media. Experiments with isolated principal cells, α-intercalated cells, and β-intercalated cells (separated by fluorescence-activated cell sorting) demonstrated that AE2 mRNA levels are comparable in the three collecting duct cell subtypes and are similarly regulated by changes in acid/base balance. Based on these results, we conclude that adaptation to changes in extracellular H+ concentration is accompanied by opposite changes in AE2 mRNA expression. The observations that AE2 mRNA is not expressed in a cell-type-specific manner and that changes in acid/base balance have similar effects on each CCD cell subtype suggest that AE2 might serve a housekeeping function rather than being the apical anion exchanger of β-intercalated cells.


Author(s):  
S.C. Huang ◽  
Y.F. Fu ◽  
Y.F. Lan ◽  
M.U. Rehman ◽  
Z.X. Tong

The purpose of the present study was to investigate the correlation between acute heat stress and relevant histopathology and biochemical parameters of kidney function. A total of 80 healthy Arbor Acer (AA) broiler chickens were randomly divided into two groups: CT (Control Temperature; 22±1°C) group and HT (High Temperature; 38±1°C) group. Histopathological images revealed alteration in kidney (renal tubular lumen dilation with tubular necrosis, especially after 10h of heat stress) of broiler chickens in HT group leading to disturbance of acid base balance. Blood urea nitrogen (BUN) and creatinine (CREA) as serum markers of renal dysfunction were elevated significantly (p less than 0.05) after 5h, and especially, after 10h of heat stress (p less than 0.01) as compared with CT group. These results indicated that the evaluation of morphological and functional parameters in kidney is required, in order to monitor broiler chickens exposed to heat stress.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Motonobu Nakamura ◽  
Ayumi Shirai ◽  
Osamu Yamazaki ◽  
Nobuhiko Satoh ◽  
Masashi Suzuki ◽  
...  

Sodium-coupled bicarbonate absorption from renal proximal tubules (PTs) plays a pivotal role in the maintenance of systemic acid/base balance. Indeed, mutations in the Na+-HCO3-cotransporter NBCe1, which mediates a majority of bicarbonate exit from PTs, cause severe proximal renal tubular acidosis associated with ocular and other extrarenal abnormalities. Sodium transport in PTs also plays an important role in the regulation of blood pressure. For example, PT transport stimulation by insulin may be involved in the pathogenesis of hypertension associated with insulin resistance. Type 1 angiotensin (Ang) II receptors in PT are critical for blood pressure homeostasis. Paradoxically, the effects of Ang II on PT transport are known to be biphasic. Unlike in other species, however, Ang II is recently shown to dose-dependently stimulate human PT transport via nitric oxide/cGMP/ERK pathway, which may represent a novel therapeutic target in human hypertension. In this paper, we will review the physiological and pathophysiological roles of PT transport.


1995 ◽  
Vol 269 (4) ◽  
pp. F551-F557 ◽  
Author(s):  
G. Fejes-Toth ◽  
E. Rusvai ◽  
K. A. Longo ◽  
A. Naray-Fejes-Toth

In addition to the gastric isoform of H-K-ATPase, the colonic isoform is also expressed in the kidney, but its intrarenal localization and exact function are not known. The goal of this study was to determine whether the colonic H-K-ATPase is expressed in the rabbit cortical collecting duct (CCD) and whether it is regulated by changes in acid/base balance. With quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) with RNA isolated from immunodissected rabbit CCD cells and degenerate oligonucleotide primers, a PCR product of the predicted size (approximately 430 bp) was amplified. The amplified DNA was further characterized by nested PCR and sequencing. Direct sequencing of the 434-bp PCR product revealed 83% identity at the nucleotide level and an 80.4% identity at the deduced amino acid level to the rat colonic H-K-ATPase. With the same primers and cDNA originating from rabbit distal colon, a DNA fragment with a size and nucleotide sequence identical to that originating from CCD cells was amplified. Furthermore, using PCR screening, we isolated and sequenced a 1.5-kb cDNA clone from a rabbit CCD library. The predicted amino acid sequence of the protein encoded by this cDNA is 85 and 82% identical to the corresponding regions of the guinea pig and rat colonic H-K-ATPase, respectively, and 70% identical to the H-K-ATPase recently cloned from Bufo marinus, whereas it shows only 45 and 42% homology to the rat Na-K-ATPase alpha 1-subunit and the rat gastric H-K-ATPase, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


1963 ◽  
Vol 41 (1) ◽  
pp. 1099-1104
Author(s):  
P. Vishwakarma

The transport of α-ketoglutaric acid along the length of the renal tubule was studied by the stop-flow method in the dog during infusion of sodium α-ketoglutarate. No deliberate attempts to change the acid–base balance were made. Under these conditions this acid was found to be excreted by a combined process of glomerular filtration and tubular reabsorption. This reabsorption was confined only to the proximal tubule. No tubular secretion was seen in any part of the nephron. The concentration gradients between the luminal urine, cell water and the plasma were measured. It was seen that the gradients between the lumen and the cell and between the lumen and the plasma were against the direction of the transport. The gradient between the plasma and the cell was favorable to the uptake of the acid by the cell. Upon consideration of these gradients, the spontaneous pH changes and the physicochemical characteristics of the molecule, the hypothesis was forwarded that an active reabsorption of α-ketoglutarate must occur in the proximal tubule from the lumen into the cell. The possibility of active transfer of this acid from the blood into the cell was also suggested.


PEDIATRICS ◽  
1968 ◽  
Vol 42 (4) ◽  
pp. 717-717
Author(s):  
Michael James Sweeney

For some years, the senior author of this book and his associates have contributed much to our understanding of the physiologic aspects of acid-base balance. The present text represents major educational effort on their part to offer a "systematic presentation of acid-base physiology in the format of programmed instruction." The primary audience the book is directed toward are those who already have the "feel" of clinical medicine and who desire "an integrated picture of acid-base physiology as a background for their clinical activities."


1986 ◽  
Vol 67 (5) ◽  
pp. 358-360
Author(s):  
S. V. Maltsev ◽  
V. M. Davydova ◽  
E. I. Zemlyakova

We examined 70 patients with metabolic nephropathy (51 with oxaluria predominance, 19 with uric acid metabolism disorders). Distribution of patients into groups was carried out according to the results of multistage research, including analysis of pedigree; repeated biochemical studies, clinical and radiological comparisons. Endogenous creatinine clearance, residual nitrogen level, urea in blood, acid-base balance were determined to characterize the functional state of the kidneys. Renal tubular function was assessed by urinary excretion of calcium, phosphates, amino acids, titratable acids, Zimnitsky's test. To detect metabolic disorders we studied uric acid content in blood and urine, oxalic acid and xanthurenic acid content in daily urine.


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