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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2017  |  Volume : 28  |  Issue : 6  |  Page : 1239-1246
Senescent chronic kidney disease: The challenges faced and the strategies to overcome


Department of Nephrology, Dhanalakshmi Srinivasan Medical College and Hospital, Trichy, Chennai Highway, Perambalur, Tamil Nadu, India

Click here for correspondence address and email

Date of Web Publication18-Dec-2017
 

   Abstract 


The management of chronic kidney disease (CKD) in elderly patients continues to pose constant challenges to clinical nephrologists. Right from the perplexing issue of calculating the glomerular filtration rate (GFR) to the confusion between the choice of disease-oriented approach and individual-centered approach, the challenges faced are mammoth. This article seeks to bring a consensus in sorting out these practical problems so that a systematic way of approach could be arrived at in managing such fragile patients. The last decade has seen an evolution and ongoing refinement of a disease-oriented approach to CKD. Since the average GFR tends to decrease with age, CKD becomes increasingly prevalent with advancing age, and thus, disproportionately elderly patients meet the criteria for CKD.

How to cite this article:
Jayaraman R, Ganapathy E, Balakrishnan S, Prashanth S, Akila R. Senescent chronic kidney disease: The challenges faced and the strategies to overcome. Saudi J Kidney Dis Transpl 2017;28:1239-46

How to cite this URL:
Jayaraman R, Ganapathy E, Balakrishnan S, Prashanth S, Akila R. Senescent chronic kidney disease: The challenges faced and the strategies to overcome. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2018 Apr 23];28:1239-46. Available from: http://www.sjkdt.org/text.asp?2017/28/6/1239/220852



   Epidemiological Facts about Elderly Chronic Kidney Disease Top


  1. Chronic kidney disease (CKD) is particularly prevalent among elderly patients
  2. As much as 30% of adults over the age of 70 years and 50% of adults aged 80 and older have abnormal renal function[1]
  3. There is a risk of 0.2–0.4% per year of an elderly person with CKD stage 3 to develop end-stage renal disease (ESRD), and the presence of concomitant proteinuria increases this risk[2]
  4. The majority of patients with CKD die before progressing to ESRD.



   Aging and Changes in the Kidneys Top


The prevalence of glomerulosclerosis increases with age; <5% of glomeruli in those one year old and 10%–30% of glomeruli in those in the 8th decade. Up to 10% of the glomeruli may be globally sclerotic in “normal” participants younger than 40 years.[3] Pathological glomerulosclerosis should be considered when the percentage of globally sclerosed glomeruli exceeds the number calculated by the formula as under:[4]

[(patient’s age in years/2) – 10].

For example, if the patient’s age is 60 years, the percentage of sclerosed glomeruli should not exceed 20%.

Many anatomical, histological, and physiological changes occur in aging kidneys. Some important changes are tabulated in [Table 1].[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] It is worth mentioning here that it is important to have knowledge on the number and percentage of sclerosed glomeruli with aging.
Table 1: Important anatomical, histological, and physiological changes in aging kidneys.

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   Estimation of the Glomerular Filtration Rate in the Elderly and the Confusion in its Interpretation: An Ever Enigmatic Concept Top


Estimation of the glomerular filtration rate (GFR) in the elderly is a key to the diagnosis and management of the highly prevalent CKD in elderly population. A near accurate GFR estimation in such patients is of paramount importance including in the prevention of drug toxicity.[18] The KDIGO guidelines recommend using the CKD Epidemiology Collaboration (CKD-EPI) equation for estimating GFR unless another equation has proved more accurate in a specific population. Therefore, this equation is now widely used; however, it was not specifically designed for elderly patients, and there were only few patients older than 70 years in the development cohort. A validated method for estimating kidney function in terms of GFR in the elderly is still lacking.

In a study by Schaeffner et al,[19] the performance of existing equations of estimated GFR including the equation employing cystatin-C along with the Berlin Initiative Study equations 1 and 2 (BIS-1 and BIS-2) was compared with the measured GFR of gold standard using iohexol; BIS-2 equation yielded the smallest bias followed by the creatinine-based BIS-1 and Cockcroft–Gault equations. All other equations considerably overestimated GFR. The BIS equations confirmed a high prevalence of persons older than 70 years with a GFR <60 mL/min per 1.73 m2 (BIS-1, 50.4%; BIS-2, 47.4%; measured GFR, 47.9%). The total misclassification rate for this criterion was smallest for the BIS-2 equation (11.6%), followed by the cystatin-C equation (15.1%).

Fehrman-Ekholm and Skeppholm[20] compared iohexol clearance with various GFR-esti-mating equations in normal elderly participants between the ages 70 and 110 years and found that the GFR had a strong correlation with age with an annual decline of 1.05 mL/ min. The modification of diet in renal disease (MDRD) formula was better associated with the GFR in the elderly while the Cockcroft–Gault equation underestimated clearance. Dowling et al[21] found that the MDRD and CKD-EPI equations significantly overestimated creatinine clearance in elderly individuals and suggested that the Cockcroft-Gault equation be used in older adults for the purpose of renal dosage adjustments as GFR overestimation by the former; two equations had the practical propensity of increasing the drug toxicity in such elderly individuals. Koppe et al,[22] compared the recently developed BIS-1 equation with the simplified MDRD and the CKD-EPI equations in a study of 224 Caucasian patients over the age of 70 years and found BIS-1 to be the most accurate. In addition, BIS-1 had the lowest median bias and the highest precision. As disease progressed, in people with CKD stages 4 and 5, the CKD-EPI equation had the highest accuracy, the lowest median bias, and the highest precision.


   HUGE Formula May be a Simple Bedside Tool to Differentiate Age-related Decline in Glomerular Filtration Rate and that due to Renal Disease Process Top


The formula takes into account the hematocrit, blood urea, and gender. It can be employed regardless of the variables of age, serum creatinine, and creatinine clearance.

L = 2.51 – (0.26 × hematocrit) + (0.12 × urea (mg/dL) (+1.38 if male).[23]

If L is negative, the decline in GFR could be presumed as a part of aging; if positive, underlying CKD is probably present.

The advantages and disadvantages of the various equations are shown in [Table 2].[19],[24],[25],[26],[27],[28]
Table 2: Salient features of various equations that could be employed for computing GFR in elderly.

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   Disease-based Approach or Individual-centered Approach? A Battle Fought for Long Top


This has served as a long-standing debate raising questionnaires to what has to be chosen as the line of path in managing such patients who present with multiple comorbidities. A disease-oriented approach focuses on prevention, diagnosis, and treatment of individual disease processes.[29],[30],[31],[32] While it provides a systematic framework for an evidence-based management, it does not give a concrete answer on how to manage frail elderly with different co-morbidities.

On the other hand, an individual-centered approach offers an advantage of aligning patient’s multitude of comorbidities with the goals and preferences in managing holistically. Below are two different cases that exemplify the importance of both the approaches in two different scenarios.

The case details are depicted in [Table 3] and [Table 4].
Table 3: Management analysis for the first case.

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Table 4: Management analysis for the second case.

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Case 1

A healthy 74-year-old woman with no comorbid conditions had a GFR of 64 mL/min/ 1.73 m2 and no proteinuria. Over several weeks, her GFR decreased to 7 mL/min/1.73 m2 with a 2+ proteinuria and red blood cell casts on urinalysis. She rapidly developed near complete anuria over a period of six days, and serologic workup was notable for the presence of a high titer of positive anti-glomerular basement antibodies. She underwent a kidney biopsy that showed pauci-immune necrotizing crescentic glomerulonephritis and was treated with plasmapheresis, cyclophosphamide, and prednisone. Her GFR returned to the baseline value, proteinuria, and hematuria resolved and has been under regular follow-up with stable renal function.

Case 2

A 82-year-old woman with advanced dementia, diabetes, hyperlipidemia, hypertension, and obesity had a GFR of 20–27 mL/min/1.73 m2 for the past four years. She stayed at home with her husband and required help with bathing, dressing, and toileting. Her husband was the primary caregiver. She was admitted to the hospital because of worsening disorientation and irritability, urinary incontinence, and anorexia. Her GFR on admission to the hospital had decreased to 16 mL/min/1.73 m2. Since her symptoms of worsening confusion and anorexia were believed to be possibly due to uremia, the patient was started on dialysis. However, these symptoms worsened after initiation of dialysis.


   Transplantation in Elderly: Exceptional Excerpts Top


Advanced age per se is not a contraindication for being a renal allograft recipient. Controlled trials have demonstrated increased survival in elderly transplanted patients than those on dialysis.

  1. Rejection rate is lower as there is blunted immune response coupled with better compliance with immunosuppressive drugs
  2. A steroid-free posttransplant immunosuppressive regimen can reduce the incidence of mortality related to cardiovascular disease and infections
  3. A pretransplant workup in an elderly patient may need a colonoscopy/barium enema as the risk of diverticulitis and colonic perforation is higher
  4. The elderly are often reluctant to turn to younger family members as potential donors, although over the past two decades, there is an increase in the percentage of live donors.


Expanded criteria donors are usually recommended for older patients (“old for old” kidney allocation). Expanded criteria donor is defined as a donor >60 years of age or donors >50 years of age with two comorbidities such as hypertension, death from cerebrovascular accident, and terminal serum creatinine >1.5 mg%.

Decreased lymphopoiesis, reduction in naive T cells, increased interferon-gamma, and decreased IL-2 production[33],[34],[35],[36] are some of the immune-related changes seen in the elderly.

Physiological changes that occur in the elderly can lead to altered pharmacokinetics of the immunosuppressants employed and need to be taken into account. Bioavailability is affected by decreased intestinal or hepatic first-pass metabolism.[37]

Lipophilic drugs such as cyclosporine can have increased volume of distribution as the relative fat content increases with age.[38] Protein binding may decrease by up to 15% to 25% in elderly individuals compared with younger adults, which can lead to increased free plasma concentrations of immunosuppressive medications.[38] This is particularly relevant in the case of mycophenolic acid, in which the free fraction represents the active inhibitory component to inosine monophosphate dehydrogenase.[39] Hypoalbuminemia may enhance the immunosuppressive effect of mycophenolic acid and its toxicity. Aging too is associated with reduced hepatic and renal clearance of most of the drugs.


   Conclusion Top


Elderly and frail individuals deserve special care and attention with respect to the management of ESRD. Special care needs to be undertaken especially those on dialysis. A holistic approach offering a perfect balance between disease-oriented and individual-based care will enable a nephrologist to treat such patients with great confidence.



 
   References Top

1.
Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third national health and nutrition examination survey. Am J Kidney Dis 2003;41:1-2.  Back to cited text no. 1
[PUBMED]    
2.
Hallan SI, Ritz E, Lydersen S, et al. Combining GFR and albuminuria to classify CKD improves prediction of ESRD. J Am Soc Nephrol 2009;20:1069-77.  Back to cited text no. 2
[PUBMED]    
3.
Lopez-Novoa JM. Mechanisms of age-associated glomerulosclerosis. In: The Aging Kidney in Health and Disease. ed. Ch 6. Springer Science and Business Media. 2008. p 114.  Back to cited text no. 3
    
4.
Smith SM, Hoy WE, Cobb L. Low incidence of glomerulosclerosis in normal kidneys. Arch Pathol Lab Med 1989;113:1253-5.  Back to cited text no. 4
[PUBMED]    
5.
Yumura W, Imasawa T, Suganuma S, et al. Accelerated tubular cell senescence in SMP30 knockout mice. Histol Histopathol 2006;21: 1151-6.  Back to cited text no. 5
[PUBMED]    
6.
Negri AL. The klotho gene: A gene predominantly expressed in the kidney is a fundamental regulator of aging and calcium/ phosphorus metabolism. J Nephrol 2005;18: 654-8.  Back to cited text no. 6
[PUBMED]    
7.
Kasiske BL, Umen AJ. The influence of age, sex, race, and body habitus on kidney weight in humans. Arch Pathol Lab Med 1986;110:55-60.  Back to cited text no. 7
[PUBMED]    
8.
Nyengaard JR, Bendtsen TF. Glomerular number and size in relation to age, kidney and body surface in normal man. Anat Rec 1992;232:194-201.  Back to cited text no. 8
[PUBMED]    
9.
Emamian SA, Nielsen MB, Pedersen JF, Ytte L. Kidney dimensions at sonography: Correlation with age, sex, and habitus in 665 adult volunteers. AJR Am J Roentgenol 1993;160: 83-6.  Back to cited text no. 9
[PUBMED]    
10.
Tauchi H, Tsuboi K, Okutomi J. Age changes in the human kidney of the different races. Gerontologia 1971;17:87-97.  Back to cited text no. 10
[PUBMED]    
11.
Wesson LG. Renal hemodynamics in physiological states. In: Wesson LG, edr. Physiology of the Human Kidney. New York: Grune & Stratton; 1969. p. 96-108.  Back to cited text no. 11
    
12.
Hollenberg NK, Adams DF, Solomon HS, et al. Senescence and the renal vasculature in normal man. Circ Res 1974;34:309-16.  Back to cited text no. 12
[PUBMED]    
13.
Kenney WL, Chiu P. Influence of age on thirst and fluid intake. Med Sci Sports Exerc 2001;33:1524-32.  Back to cited text no. 13
[PUBMED]    
14.
Schoeller DA. Changes in total body water with age. Am J Clin Nutr 1989;50:1176-81.  Back to cited text no. 14
[PUBMED]    
15.
Lerma EV. Anatomic and physiologic changes of the aging kidney. Clin Geriatr Med 2009;25:325-9.  Back to cited text no. 15
[PUBMED]    
16.
Perazella MA, Mahnensmith RL. Hyperkalemia in the elderly: Drugs exacerbate impaired potassium homeostasis. J Gen Intern Med 1997;12:646-56.  Back to cited text no. 16
[PUBMED]    
17.
Berliner N. Anemia in the elderly. Trans Am Clin Climatol Assoc 2013;124:230-7.  Back to cited text no. 17
[PUBMED]    
18.
Garasto S, Fusco S, Corica F, et al. Estimating glomerular filtration rate in older people. Biomed Res Int 2014;2014:916542.  Back to cited text no. 18
[PUBMED]    
19.
Schaeffner ES, Ebert N, Delanaye P. Two novel equations to estimate kidney function in persons aged 70 years or older. Ann Int Med 2012;157:471-81.  Back to cited text no. 19
    
20.
Fehrman-Ekholm I, Skeppholm L. Renal function in the elderly (>70 years old) measured by means of iohexol clearance, serum creatinine, serum urea and estimated clearance. Scand J Urol Nephrol 2004;38:73-7.  Back to cited text no. 20
[PUBMED]    
21.
Dowling TC, Wang ES, Ferrucci L, Sorkin JD. Glomerular filtration rate equations overestimate creatinine clearance in older individuals enrolled in the baltimore longitudinal study on aging: Impact on renal drug dosing. Pharmaco-therapy 2013;33:912-21.  Back to cited text no. 21
    
22.
Koppe L, Klich A, Dubourg L, Ecochard R, Hadj-Aissa A. Performance of creatinine-based equations compared in older patients. J Nephrol 2013;26:716-23.  Back to cited text no. 22
[PUBMED]    
23.
Alvarez-Gregori JA, Robles NR, Mena C, et al. The value of a formula including haematocrit, blood urea and gender (HUGE) as a screening test for chronic renal insufficiency. J Nutr Health Aging 2011;15:480-4.  Back to cited text no. 23
[PUBMED]    
24.
Michels WM, Grootendorst DC, Verduijn M, et al. Performance of the cockcroft-gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol 2010;5:1003-9.  Back to cited text no. 24
[PUBMED]    
25.
Stevens LA, Coresh J, Feldman HI, Greene T, Lash JP, Nelson RG. Evaluation of the modification of diet in renal disease study equation in a large diverse population. J Am Soc Nephrol 2007;18:2749-57.  Back to cited text no. 25
    
26.
Finney H, Bates CJ, Price CP. Plasma cystatin C determinations in a healthy elderly population. Arch Gerontol Geriatr 1999;29:75-94.  Back to cited text no. 26
[PUBMED]    
27.
Fliser D, Ritz E. Serum cystatin C concentration as a marker of renal dysfunction in the elderly. Am J Kidney Dis 2001;37:79-83.  Back to cited text no. 27
[PUBMED]    
28.
Séronie-Vivien S, Delanaye P, Piéroni L, et al. Cystatin C: Current position and future prospects. Clin Chem Lab Med 2008;46:1664-86.  Back to cited text no. 28
    
29.
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1-266.  Back to cited text no. 29
[PUBMED]    
30.
National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42:S1-201.  Back to cited text no. 30
[PUBMED]    
31.
Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004;43:S1-290.  Back to cited text no. 31
[PUBMED]    
32.
Muller-Sieburg C, Sieburg HB. Stem cell aging: Survival of the laziest? Cell Cycle 2008;7:3798-804.  Back to cited text no. 32
[PUBMED]    
33.
Muller-Sieburg CE, Cho RH, Karlsson L, Huang JF, Sieburg HB. Myeloid-biased hematopoietic stem cells have extensive selfrenewal capacity but generate diminished lymphoid progeny with impaired IL-7 responsiveness. Blood 2004;103:4111-8.  Back to cited text no. 33
[PUBMED]    
34.
Cho RH, Sieburg HB, Muller-Sieburg CE. A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells. Blood 2008;111:5553-61.  Back to cited text no. 34
[PUBMED]    
35.
Castle SC, Uyemura K, Crawford W, et al. Age-related impaired proliferation of peripheral blood mononuclear cells is associated with an increase in both IL-10 and IL-12. Exp Gerontol 1999;34:243-52.  Back to cited text no. 35
[PUBMED]    
36.
Turnheim K. Drug dosage in the elderly. Is it rational? Drugs Aging 1998;13:357-79.  Back to cited text no. 36
[PUBMED]    
37.
Danovitch GM, Gill J, Bunnapradist S. Immunosuppression of the elderly kidney transplant recipient. Transplantation 2007;84: 285-91.  Back to cited text no. 37
[PUBMED]    
38.
Schmucker DL. Liver function and phase I drug metabolism in the elderly: A paradox. Drugs Aging 2001;18:837-51.  Back to cited text no. 38
[PUBMED]    
39.
Nowak I, Shaw LM. Mycophenolic acid binding to human serum albumin: characterization and relation to pharmacodynamics. Clin Chem 1995;41:1011-7.  Back to cited text no. 39
    

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Correspondence Address:
Rajesh Jayaraman
Department of Nephrology, Dhanalakshmi Srinivasan Medical College and Hospital, Peramabalur, Tamil Nadu
India
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DOI: 10.4103/1319-2442.220852

PMID: 29265034

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