Renal concentrating capacity as a marker for glomerular filtration rate : Renal concentrating capacity as marker for GFR

We reexamined the relationship between creatinine clearance (Ccr) and body habitus in 212 girls and 356 boys, including 181 boys and 69 girls between 13 and 21 years of age. The use of formula Ccr = k L/Pcr, where k = 0.55 for the calculation of GFR, resulted in a significant underestimation of GFR in adolescent boys but was suitable for girls. In 51 adolescent boys the equation Ccr = 0.7 L/Pcr resulted in an accurate estimate of GFR. Regression analysis in 133 boys aged 3 to 21 years showed that the constant k increased gradually and linearly with age (r = 0.35, P less than 0.01). GFR could be better estimated for boys of any age by the linear bivariate equation Ccr = 1.5 (age) + 0.5 (L/Pcr), where age is given in years (r = 0.82, P less than 0.001). This equation yielded slightly better results than did 0.7 L/Pcr in 91 additional clearance studies performed in adolescent boys with native kidneys or functioning renal transplants. The larger value for the constant k (0.7) and the age correction for GFR reflect the greater rate of urinary creatine excretion (and thus muscle mass) per unit of body mass in adolescent boys.

This is an editorial review of investigations into the correlation of structure and function of the kidney in various inflammatory and noninflammatory glomerular diseases and in focal and diffuse interstitial nephritis. In detail these investigations produced the following results: (1) The excretory function of the glomeruli for substances usually eliminated with the urine is, in the case of inflammatory and noninflammatory glomerular diseases, detrimentally affected by tubulointerstitial changes, i.e. by processes accompanied by interstitial fibrosis and tubular atrophy. Likewise primary interstitial renal diseases when accompanied by interstitial fibrosis and tubular atrophy may lead to reduction in GFR. (2) Inflammatory and noninflammatory glomerular diseases, even when very severe, are not accompanied by a measurable reduction in GFR when the renal cortex interstitium shows no changes and the tubules exhibit no pathological findings. (3) The concentration ability of the kidney, too, depends primarily on tubulointerstitial changes and not primarily on a reduction of the glomerular filtration surface area. As interstitial fibrosis and tubular atrophy increase, the maximum concentration ability of the kidney decreases, even when the glomerular structure is preserved. (4) The decrease in GFR in the case of processes in the renal cortex accompanied by severe interstitial fibrosis is the result of the reduction of the number and of the area of the postglomerular vessels, i.e. the result of an impeded outflow from the glomeruli and of a concomitant slower circulation through the glomeruli. (5) In the case of inflammatory and noninflammatory glomerular and extraglomerular renal diseases accompanied by slight interstitial fibrosis and tubular atrophy, the GFR is detrimentally affected via a hormonally controlled self-regulating mechanism (Thurau-mechanism) in the form as modified by Baumbach and Skott and Leyssac. The glomerular function thereby adapts to an insufficient tubular function, without there necessarily being any structural changes in the glomeruli.

Studies were performed to determine the mechanism underlying deficient arginine vasopressin (AVP)-stimulated adenylyl cyclase activity in chronic renal failure (CRF). As compared to control, principal cells cultured from the inner medullary collecting tubule of rats previously made uremic by 5/6 nephrectomy fail to accumulate cAMP when stimulated with AVP. CRF cells do respond normally to forskolin or cholera toxin and the defect in AVP responsiveness is not prevented by treatment with pertussis toxin, by cyclooxygenase inhibition, or by inhibition or down-regulation of protein kinase C. In contrast to their lack of responsiveness to AVP, CRF cells respond normally to other agonists of adenylyl cyclase such as isoproterenol or prostaglandin E2. Plasma membranes prepared from the inner medullae of CRF rats exhibit a marked decrease in apparent AVP receptor number but no change in the apparent number of beta adrenergic receptors. Reverse transcriptase PCR of total RNA from the inner medullae of CRF animals reveals virtual absence of V2 receptor mRNA; mRNA for alpha s is present in normal abundance. These studies indicate that AVP resistance in CRF is due, at least in part, to selective down-regulation of the V2 receptor as a consequence of decreased V2 receptor mRNA.