Aging & Renal Disease: Introduction
As the elderly population continues to grow, the diagnosis and treatment of renal diseases become challenges for the everyday nephrology practice. Although elderly patients are prone to the same diseases of the kidney as younger patients, the diagnostic criteria are not so clearly defined. Anatomic and functional age-induced changes often overlap pathologic processes. The resulting reduced renal function decreases the individual’s capacity to respond to a variety of stresses and has important clinical implications for diagnosis and treatment. Comorbid conditions, the absence of classic symptoms, “symptomless” conditions in those with impaired consciousness, and the poor correlation between clinical presentation and the etiology of disease make the diagnosis of renal diseases in the elderly even more difficult. Finally, several pathologic conditions of the kidneys might occur simultaneously in the elderly.
Acute Renal Failure
Acute renal failure (ARF) is more frequent in elderly patients than in younger patients and it is often due to multiple causes. Predisposing factors are age-related changes in renal structure and function. The incidence of ARF is estimated to involve 6–10% of all admissions of the elderly to an acute medical service.
The most frequent causes of ARF are nephrotoxic drugs, sepsis, and hypoperfusion. Radiocontrast-induced ARF and postoperative ARF are still very frequent (occurring in about 17% and 25% of cases, respectively).
About 50% of the patients with ARF have a prerenal etiology and the majority of them have only mild renal impairment. Oliguria is not a prominent finding in ARF in the elderly and cases of nonoliguric ARF may go unrecognized. This may result in overdosing patients with renally excreted medications (digitalis, gentamicin). Hypophosphatemia and hypokalemia, when present, most probably reflect the severity of the underlying disease or malnutrition.
The treatment of patients with ARF requires careful monitoring of fluid and electrolyte balance. It is very important to prevent malnutrition since hypercatabolism is a frequent finding in elderly patients with ARF; nutritional support should be implemented during the early phase since such patients may lose about 0.5 kg of body mass per day. On the other hand, fluid restriction will delay recovery from ARF and lead to a deterioration in central nervous system function. In patients with advanced renal failure standard dialytic techniques including slow continuous methods should be applied.
The prognosis differs depending on the underlying disease since age itself does not have a significant impact on the prognosis of patients with ARF. The aged kidney retains the capacity to recover from acute ischemic or toxic injury over several weeks. However, care should be taken to avoid nephrotoxins, radiocontrast agents, and volume depletion. The overall mortality rates correlate with the severity of clinical disease ranging between 40% and 60%. Aortic aneurysm repair had very high mortality (as high as 100% in some series) but recent introduction of endovascular repair has decreased this substantially. Other causes of acute renal failure such as hepatic failure, shock, and renovascular disease also have high mortality. Patients with intrinsic renal failure had a higher than expected mortality rate possibly because of delays in diagnosis. A higher mortality rate was also seen in obstructive uropathy in the elderly, which is caused by malignant diseases more often than in younger patients. The prognosis is negatively influenced by malnutrition and high urea and creatinine levels. Of those patients who survive to discharge, about 60% have complete recovery of renal function and the remaining have some degree of renal impairment not requiring dialysis.
Glomerular Diseases
Glomerular diseases have a similar or slightly higher incidence in the elderly than in younger adults. The disease spectrum is similar to that in younger populations with the main presenting features being proteinuria and hematuria.
Renal biopsy, as a diagnostic marker, remains the gold standard for diagnosis, with no significant increase in complication rates as compared to younger patients. Still, some age-related differences exist with regard to difficulties in distinguishing lesions of chronic ischemia from previous proliferative glomerulonephritis (GN) and focal sclerosing GN. Elderly patients who undergo renal biopsy have a greater incidence of nephrotic syndrome or acute renal failure than younger patients: Idiopathic GN is the most common underlying diagnosis followed by secondary GN and unclassified GN.
Nephrotic syndrome is the most common reason for renal biopsy in the elderly. The underlying reasons include membranous nephropathy (an almost three times higher incidence than in the overall population), minimal change disease (MCD), amyloidosis, and multiple myeloma. Focal segmental glomerulosclerosis and immunoglobulin A (IgA) nephropathy are less common than in younger patients.
Out of all cases of membranous nephropathy in the elderly, about 80% are idiopathic and 20% are secondary to solid organ tumors and drugs.
A full clinical examination, chest x-ray, CT scan of the abdomen, and stool examination should be performed as screening tests. Apart from nephrotic proteinuria, which is a usual finding, elderly patients have hypertension, hematuria, and renal impairment at the time of biopsy more frequently than younger patients.
Treatment with prednisone and chlorambucil has a favorable effect, but remission rates were lower, the time to remission was longer, and the severity of side effects was higher. The recommended dose of chlorambucil is 0.1 mg/kg/day for 3–6 months with or without low-dose corticosteroids.
The typical presentation of minimal change nephropathy (MCN) in elderly patients is nephritic syndrome. Again, microscopic hematuria, hypertension, and renal impairment are more frequent at the time of presentation than in younger patients.
Complications resulting from hypoalbuminemia, hyperlipidemia, and hypercoagulability include thrombotic events, infections, and progressive cardiovascular disease.
Treatment with a standard immunosuppressive regimen can be used, but for a longer duration than in younger patients. Corticosteroid-resistant patients may benefit from chlorambucil, cyclophosphamide, or cyclosporine A, but with a risk of bone marrow depression.
This is not the usual form of glomerulonephritis in the elderly.
Heavy proteinuria is a typical presentation of disease, which is often associated with some degree of renal impairment.
A trial of corticosteroids for 3 months (or even an additional 3 months if there is no response) should be considered. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have an antiproteinuric effect and should be used either before trial of steroids or simultaneously with steroids.
Immune complex deposition, antineutrophylic cytoplasmic antibody (ANCA), and antiglomerular basement membrane (anti-GBM) antibodies may cause proliferative GN with the clinical findings and course of disease similar to those found in younger patients. Elderly patients tend to present with much higher serum creatinine levels and a higher incidence of hypertension and refractory renal impairment. Standard immunosuppressive therapy in elderly patients appears to be as effective as in younger patients in terms of short-term prognosis, but there is a higher risk of complications with immunosuppression.
Crescentic GN can be associated with immune deposits (as seen in severe IgA nephropathy or lupus nephritis) or with pauci-immune disease without immune deposits (Wegener’s granulomatosis, anti-GBM disease, and polyarteritis nodosa). The clinical presentation includes nausea, anorexia, malaise, edema, arthralgia, and myalgia. Symptoms of pyrexia, rash, and hemoptysis suggest a diagnosis of vasculitis. Renal manifestations include hematuria (microscopic or macroscopic), hypertension, and oliguria. Serum ANCA levels, anti-GBM levels, antinuclear factor, complement, immunoglobulin levels, and renal biopsy help distinguishing the different syndromes.
A standard immunosuppressive regimen with steroids and cyclophosphamide is indicated.
As in the overall population, glomerular diseases are associated with diabetes, myeloma, systemic lupus erythematosus, and systemic bacterial infections and no specific findings for elderly patients have been described compared to younger patients.
Acute poststreptococcal glomerulonephritis (APSGN) originates more often from pyodermal than from throat infection. Therefore antideoxyribonuclease B is a more specific test than antistreptolysin O titer in elderly patients with APSGN. Oliguria is a more frequent finding most probably because of underlying age-related renal changes. The outcome of disease is similar to that in younger patients and most patients recover renal function.
Renovascular Disease
Ischemic nephropathy (or insufficient renal perfusion) includes two entities: Renal macrovascular disease or renal artery stenosis (RAS) and microvascular diseases, which affect intrarenal arteries.
The prevalence of RAS is difficult to estimate, but according to some data age is a significant multivariate predictor for RAS (>50%). The prevalence of significant RAS is ∼50% in hypertensive patients >55 years of age who have coexistent coronary artery disease (CAD) or peripheral vascular disease (PVD). The risk factors include age, hypertension, diabetes, and evidence of vascular disease elsewhere in the body.
Disease should be suspected in patients who have flash pulmonary edema, unresponsive hypertension, and generalized vascular disease, in those who develop ARF after mild hypotension or with use of ACEIs or ARBs, and in cases of renal impairment of unknown etiology.
Diagnostic procedures include duplex ultrasonography, captopril renal scintigraphy, and magnetic resonance (MR) and computed tomographic (CT) angiography using the gold standard of intra-arterial angiography.
The disease is often undetected and if left untreated stenosis will progress over a few years.
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