Evaluation and Management of Nephrolithiasis in the Aging Population With Chronic Kidney Disease

Anna L Zisman; Fredric L Coe; Elaine M Worcester

Disclosures

Aging Health. 2011;7(3):423-433. 

In This Article

Impact of Aging on Treatment of Stone Disease

Medical Treatment

Volume The mainstay of primary and secondary prevention of stone disease is high urinary volume, achieved by increasing oral fluid intake. Generally at least 2.5–3 L of urine volume is necessary throughout the day. When treating elderly patients, or patients with CKD, one must be cognizant of the potential adverse effects of water loading. The elderly, for example, may have an impaired ability to excrete a water load,[66,67] which may lead to fluid retention and worsening of other underlying disease states such as congestive heart failure, liver disease or lung disease. Impaired capacity for water excretion is also a feature of CKD, which can lead to similar complications.[68] In addition, a post hoc analysis of the Modification of Diet in Renal Disease (MDRD) study has noted a potentially increased risk of CKD progression with increasing urinary volume,[69] though at this time there does not appear to be any corroborating evidence to alter established practice.

Thiazide Diuretics In patients with calcium oxalate stones, hypercalciuria is often an underlying disorder, which also contributes to bone loss in this patient population. Thiazide diuretics are generally a safe and effective treatment option for hypercalciuria;[70] however prescribers must exercise caution with thiazide use in the elderly and in patients with CKD. There is evidence for an increased risk of hyponatremia in the elderly on thiazide therapy owing to an underlying impaired ability to excrete a free water load.[71] Furthermore, a recent study noted a 25% increased risk of falls in the 3 weeks after initiation of thiazide therapy,[72] presumably secondary to orthostatic hypotension. However, it is also important to note that long-term thiazide use has been associated with higher BMD[73] and decreased risk of hip fracture in the elderly[74] so, as with any patient, careful consideration of the risks and benefits of therapy is prudent. Thiazide use in CKD is limited by decreased efficacy with GFR <30 ml/min/1.73 m2.[20]

Alkalinizing Agents Alkali supplementation is a mainstay of therapy in uric acid nephrolithiasis,[75] which may be seen in the older population owing to the increased burden of diabetes, obesity and the metabolic syndrome, which are all associated with low urinary pH.[76] Furthermore, hypocitraturia, a common metabolic abnormality in the older stone former,[21] also responds to urinary alkalinization. Most commonly, potassium citrate is the alkalinizing agent of choice secondary to its favorable side-effect profile. Its mechanism of action is via conversion of citrate to bicarbonate by the liver, subsequently promoting bicarbonaturia with an associated rise in the urine pH. As the citrate is complexed with potassium, prescribers must be cautious to avoid hyperkalemia, which is often more difficult in the older patient, and particularly the older patient with CKD. The elderly suffer from comorbid conditions such as hypertension and heart failure and are often receiving concomitant therapy with agents targeting the renin–angiontensin system. Impairment of the renin–angiontensin system via commonly prescribed agents such as spironolactone, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers impedes the renal excretion of potassium and may cause life-threatening hyperkalemia in the setting of potassium loading. An alternate alkalinizing agent is sodium bicarbonate, which is also typically well tolerated but can be associated with significant bloating. High doses of sodium bicarbonate are required to achieve a meaningful rise in urine pH, which results in sodium loading of approximately 40–50 mEq per day. There is some concern that this can exacerbate hypertension, if present, owing to increased fluid retention. However, there is reasonable evidence that it is the chloride component of salt that accounts for the hypertension.[77] Of greater concern in the management of stone disease is the potential for increased calcium excretion with sodium excess, which can also increase risk of stone disease.[78]

Allopurinol As mentioned previously, urinary alkalinization is the primary approach to the management of uric acid nephrolithiasis. However, if patients are unable to tolerate therapy with potassium citrate or sodium bicarbonate, have recurrent gouty symptoms, or their urine remains supersaturated with regard to uric acid despite urinary alkalinization and increased urine volume, allopurinol may be used as an adjunct treatment. However, it should be noted that allopurinol has never been shown in a randomized controlled trial to be effective in preventing recurrent nephrolithiasis in patients with uric acid stones; its only clearly proven benefit in nephrolithiasis prevention is in uricosuric patients with calcium oxalate stone disease.[79] Allopurinol dosing must be carefully monitored in the elderly, particularly those with CKD, as decreased doses must be administered due to the diminished renal function. One alternative is febuxostat, a newer xanthine oxidase inhibitor that is at least as effective as allopurinol in lowering serum uric acid levels[80] but does not require dose adjustment for renal impairment.[81] The impact of febuxostat on prevention of recurrent nephrolithiasis in patients with either uric acid stones or hyperuricosuria and calcium oxalate stones is unknown.

Surgical Treatment

As the population ages, nephrologists and urologists will be faced with the question of optimal surgical management for stone disease in the elderly. It is important to consider the older patient group separately, as treatment is generally less successful in this population. For example, multiple studies have shown that the stone-free rate (SFR) is significantly lower in those 60 years of age or older treated with extracorporeal shockwave lithotripsy (ESWL), compared with their younger counterparts. In one of the earliest reports to address the question, Ackermann and colleagues analyzed SFR outcomes in a multivariate analysis in 160 patients undergoing lithotripsy for a single stone.[82] Patients over 60 years of age had a significantly decreased SFR with treatment relative to their younger counterparts. In another analysis of nearly 3000 patients undergoing ESWL for nephrolithiasis, patients over 40 years of age demonstrated an SFR of 84%, compared with an SFR of 89% in patients under the age of 40 years.[83] In the largest and most detailed analysis to date to address the question of age as a contributor to ESWL outcomes, Ng et al. evaluated the SFRs for 2192 patients undergoing ESWL stratified by age groups: age <40 years, 41–60 years, and >60 years.[84] SFRs were 54.0, 43.0 and 37.6%, respectively, for the three age groups. Interestingly, when the authors separated the patients into two groups – patients with ureteric stones and patients with renal stones – it was only the patients with renal stones that demonstrated the worse outcomes compared with their younger counterparts. This lack of demonstrable differences in outcomes for ureteral stones has been confirmed by others as well.[85] One proposed hypothesis suggests this discrepancy in success rates is secondary to a greater degree of glomerulosclerosis in the aging kidney, which decreases the potency of the sound waves emitted by the lithotripter,[86] but does not affect the success rates for ureteral stones.

Besides the lower success rates in the older population, the literature also suggests a greater incidence of complications with ESWL in elderly patients. Although generally felt to be a benign procedure, in the general population ESWL has been associated with increased incidence of perinephric and intrarenal hematoma. For example, in a report of 50 patients who underwent computed tomography pre- and post-ESWL, subcapsular hematomas were found in 15% and intrarenal hematomas were noted in 4%. Kidneys subjected to lithotripsy were approximately 10% larger after treatment, and 70% of patients demonstrated perinephric soft tissue stranding after the procedure.[87] The elderly seem to be particularly at risk, as noted in a series of 415 electromagnetic shock wave lithotripsies in 317 patients.[88] Subcapsular or perinephric hematomas developed in 4.1% of cases, with the risk of hematoma increasing by 67% with each decade. In a different trial addressing risks of ESWL, asymptomatic patients with lower pole stones were prospectively enrolled and randomized to percutaneous nephrolithotomy (PCNL), ESWL or conservative management. After treatment, subjects underwent renal scintigraphy with scarring noted in 16% of patients receiving ESWL, compared with 3.2% in the PCNL group.[89] In another study, the authors evaluated the resistive index after kidneys had received ESWL, with 30% of kidneys demonstrating an elevated resistive index.[90] Interestingly, all of the patients found to have higher resistive indices were greater than 60 years of age.[90] In an important follow-up study, the investigators tracked 57 of the 76 patients initially enrolled for over 2 years, and demonstrated persistent elevations in the resistive indices in 30% of patients.[91] Similarly, only patients over 60 years of age demonstrated the abnormal renal vascular resistance, with 75% of these patients showing pathologic levels, suggesting the presence of permanent renal damage.[91] These investigators also noted new-onset hypertension in 17.5% of their study population, which disproportionately affected the elderly group (45%). Notably, all patients who developed hypertension showed evidence of elevated resistive indices immediately after the procedure and demonstrated progressive increases in these values over the ensuing 2 years. Support for the concept of renal injury and hypertension related to ESWL also comes from epidemiologic data. In one cohort of patients followed for almost 20 years, there was a significantly increased risk of hypertension after ESWL.[92] However, the same authors failed to demonstrate the same risk profile in another cohort.[93]

In addition to increasing concerns regarding safety of ESWL in the elderly, ESWL appears to be less effective in patients with CKD. Lee et al. noted a decreased stone-free rate after lithotripsy for proximal ureteral stones in patients with eGFR <60 ml/min.[94] The authors also noted ESWL to be less successful for all stone locations in patients with a serum creatinine >2 mg/dl.[94] In this report patients with CKD were also more likely to require additional interventions such as ureteroscopic stone retrieval.[94]

Given the concerns surrounding ESWL in the older population, alternate treatment options include PCNL and ureteroscopy.[95] In a recent paper, Anagnostou et al. reviewed the outcomes for PCNL on 779 patients divided into two age groups: 17–69 years and >70 years of age.[96] No differences were noted in adverse events between the two groups, though there appeared to be a trend towards improved outcomes in the younger population (p = 0.051). Overall PCNL seems to be highly successful and safe, with more then 85% of patients suffering no decrement to their pre-PCNL eGFR postprocedure.[97] For example, in a series of patients where nearly half had at least stage 3 CKD, the eGFR at 1 year increased from 45 to 50 ml/min.[98] However, in another report that tracked patients over 4 years, up to a quarter of the patients experienced a decline in renal function, with patients with diabetes, single kidney and infectious complications found to be at highest risk for progression.[99] In addition to the potential long-term sequelae, acute complications of PCNL can include blood loss, sepsis, renal scarring and perforation of a renal pelvis.

Given the issues previously outlined, we favor ureteroscopic management of stone disease as the initial approach in older patients with CKD whenever possible. Although complications of ureteroscopy can include ureteral injury, ureteral or urethral stricture and sepsis,[100] it is generally a well-tolerated procedure and one that can be performed safely in patients receiving anticoagulation or antiplatelet agents,[101] which is of greater importance in the geriatric population. In a key paper, Turna et al. compared the surgical outcomes of 37 patients receiving either warfarin, aspirin or clopidogrel who underwent ureteroscopy with holmium: YAG laser lithotripsy for management of intrarenal stones to a group of 37 patients matched for stone size, location and total stone burden but who were not anticoagulated.[101] Intraoperative visibility was not compromised in any anticoagulated patient, and no blood transfusions were required in either group as no hemorrhagic complications were noted. At 1 month postoperatively, the stone-free rates were similar between the two groups.

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