Mechanisms of renal tubular defects in old age

Dontas, A. S.; Marketos, S.; Papanayiotou, P.

doi:10.1136/pgmj.48.559.295

Cited by 90 publications

(42 citation statements)

References 18 publications

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“…It has been demonstrated that both age and vascular disease correlate independently with the percentage of hyalinized glomeruli in the aged [13]. Indeed, in some studies the renal blood flow declined progressively at a rate of approximately 10% per decade, starting after the 4th decade [5,20].…”

Section: Anatomy and Physiologymentioning

confidence: 99%

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Age-Dependent Changes of the Kidneys: Pharmacological Implications

Mühlberg

Platt²

1999

Gerontology

225

105

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About 40% of the intoxications after drug administration occur in the elderly. A significant proportion of the disease states in elderly patients is related to adverse reactions to prescribed drugs. Declining renal function, a reduction in both renal blood flow and glomerular filtration rate, is a major contributor to drug toxicity in the elderly. Therefore, a review (based on newer papers from Medline) of age-dependent changes of the kidneys and their consequences for drug therapy in geriatric patients is presented. Renal changes that occur with aging are: a decrease of renal weight, a thickening of the intrarenal vascular intima, sclerogenous changes of the glomeruli, and infiltration of chronic inflammatory cells and fibrosis in the stroma. Altered renal tubular function, including impaired handling of water, sodium, acid, and glucose, is also frequently present in old age. Impaired ‘endocrinologic’ functioning manifested by changes of the renin-angiotensin system, vitamin D metabolism, and antidiuretic hormone responsiveness has been reported. The aging kidney is constantly exposed to the effects of a variety of potential toxic processes, i.e., drugs and chronic illnesses including hypertension, diabetes, and atherosclerotic disease. Renal changes that occur with aging also consist of impairment in the ability to concentrate urine and to conserve sodium and water. These physiological changes increase the risks of volume depletion and prerenal type of acute renal failure. A frequent cause of acute renal failure in the elderly is drug-induced nephropathy. Nonsteroidal anti-inflammatory drugs, antibiotics, and diuretics are most often involved. Due to the age-dependent decline of renal function, the pharmacokinetics of many drugs are altered in elderly patients. Therefore, the most important renal function to monitor with aging is the creatinine clearance. Changes in pharmacokinetics of many drugs and most decisions on drug dosage can be based on this information alone, as tubular functions of the kidney decrease at rates paralleling the age-dependent decrease in glomerular filtration rate (which is approximately measured by the creatinine clearance). As a conclusion, age-dependent changes of renal function are not only responsible for changes in pharmacokinetics and pharmacodynamics. In many cases, the kidneys are the target organ of adverse drug reactions too.

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Section: Anatomy and Physiologymentioning

confidence: 99%

“…The proximal tubular volume of individual nephrons tends to decrease from a mean of 0.076 mm 3 at 20-39 years to a mean of 0.059 mm 3 at 80-101 years [12]. Since the loss of the glomerular mass is proportional to the loss of the tubular mass, the glomerulotubular balance is, in general, well preserved [5,13].…”

Section: Anatomy and Physiologymentioning

confidence: 99%

Age-Dependent Changes of the Kidneys: Pharmacological Implications

Mühlberg

Platt²

1999

Gerontology

225

105

View full text Add to dashboard Cite

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“…Loss of nephrons in the aging kidney that result in an obligatory solute diuresis and an intrinsic defect in solute transport in the diluting segment of the nephron impose inherent restrictions on the minimal osmolality that the renal tubule can establish. 38 Although the ability to excrete an acute salt and water load is dependent on factors intrinsic to the kidney, overwhelmingly so is the ability to suppress antidiuretic hormone release and maintain a waterimpermeable segment in the terminal nephron. Thus, an inappropriate, nonosmotic release of antidiuretic hormone that is common to sick elderly patients, coupled with an intrinsic defect in urinary dilution and a decline in glomerular filtration, will also potentiate excessive water retention and predispose to the prolonged overexpansion of extracellular water seen in elderly, critically ill patients.…”

Section: Commentmentioning

confidence: 99%

Prolonged Overexpansion of Extracellular Water in Elderly Patients With Sepsis

Cheng

Plank²,

Hill³

1998

Arch Surg

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“…A potent COX-1 and COX-2 inhibitor as indomethacin was markedly decreased in the synthesis of vasodilatory PG in a renal ablation model than a selective COX-2 inhibitor (7). In elderly patients, renal blood flow (24,25) and urinary PGI 2 excretion (26) were decreased. Taken together with these findings, short-term administration of DF, but not LP induced renal ischemia, as a result, the renal function was impaired in elderly patients after LRN.…”

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confidence: 99%

Short-term Administration of Diclofenac Sodium Affects Renal Function After Laparoscopic Radical Nephrectomy in Elderly Patients

Mizuno

Ito

Miyagawa

et al. 2012

Japanese Journal of Clinical Oncology

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Objective: Non-steroidal anti-inflammatory drugs decrease the glomerular filtration rate. However, few studies have been conducted on renal function in patients treated with nonsteroidal anti-inflammatory drugs during the first week after laparoscopic radical nephrectomy. The purpose of this study is to determine whether short-term administration of non-steroidal anti-inflammatory drugs during the first week after laparoscopic radical nephrectomy is a risk factor for impaired renal function. Methods: Renal carcinoma patients undergoing laparoscopic radical nephrectomy in Nagoya University Hospital from April 2004 to July 2010 were identified in a retrospective cohort study. The 164 patients were divided into non-non-steroidal anti-inflammatory drug-treated (n ¼ 50) and non-steroidal anti-inflammatory drug-treated (n ¼ 114) groups. Results: Elderly patients (.60 years old) in the non-steroidal anti-inflammatory drug-treated group showed a significant correlation between the residual renal function ratio and the total dose of diclofenac sodium (r ¼ 20.277, P , 0.05). There was no significant correlation between the residual renal function ratio and the total dose of loxoprofen sodium. The time to doubling of the serum creatinine level was significantly shorter in elderly patients treated with diclofenac sodium compared with that in patients treated with non-non-steroidal anti-inflammatory drugs (P ¼ 0.034). These results suggest that renal ischemia induced by short-term administration of diclofenac sodium impairs renal function in elderly patients after laparoscopic radical nephrectomy. Conclusions: In the present study, we found the first evidence that short-term administration of diclofenac sodium is one risk factor for renal impairment after laparoscopic radical nephrectomy in elderly patients. To prevent renal impairment after laparoscopic radical nephrectomy in elderly patients, the use of loxoprofen sodium, which has a negligible effect on renal function compared with diclofenac sodium, is recommended.

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Mechanisms of renal tubular defects in old age

Cited by 90 publications

References 18 publications

Age-Dependent Changes of the Kidneys: Pharmacological Implications

Age-Dependent Changes of the Kidneys: Pharmacological Implications

Prolonged Overexpansion of Extracellular Water in Elderly Patients With Sepsis

Short-term Administration of Diclofenac Sodium Affects Renal Function After Laparoscopic Radical Nephrectomy in Elderly Patients

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