|Year : 2008 | Volume
| Issue : 4 | Page : 669-677
|Dilemma of Renal Disease in Elderly
Abdel Basset El Essawy1, Dujanah Mousa2, Mohamed Al-Sulaiman2
1 Nephrology Unit, New Damietta Al-Azhar University Hospital and Faculty of Medicine, Mansoura Urology and Nephrology Center, Mansoura, Egypt
2 Department of Nephrology, Armed Forces Hospital, Riyadh, Saudi Arabia
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| Abstract|| |
The aging process results in profound anatomic and functional changes in a number of human body systems. Changes in kidney function with normal aging are the most dramatic of any human organ or organ system. These include anatomical, physiological, hemodynamic and immunological changes. Increased propensities of systemic diseases and exposure to poly-pharmacy of the aged group have an additive deleterious effect. The aforementioned changes have its implications on clinical presentations, management and prognosis of all renal diseases in elderly. Atypical presentation, more frequent and longer course are the characteristics of acute renal failure in this age group. Also, presentation of glomerular diseases, clinical course, prognosis, decision of performing a renal biopsy and use of immunosuppressive drugs in elderly specially those subgroup above 80 years of age are still a big challenges that needs a consensus and standardization.
|How to cite this article:|
El Essawy AB, Mousa D, Al-Sulaiman M. Dilemma of Renal Disease in Elderly. Saudi J Kidney Dis Transpl 2008;19:669-77
| Introduction|| |
Membrano-Proliferative Glomerulonephritis (MPGN) is an uncommon cause of glomerular disease that, in its idiopathic form, primarily occurs between the ages of 8 and 30 years. ,, It was reported to be between 2.6-4.9% among elderly with glomerular disease. ,,, Acute renal failure (ARF) has been reported as a complication in patients with minimal change and focal segmental glomerulosclerosis with increased risk in males, older individuals, and those with hypertension, lower serum albumin levels and greater proteinuria. ,, ARF has rarely been described in patients with membranous nephropathy.  We report an elderly patient with MPGN presented initially with ARF.
| Case Presentation|| |
An 81-year-old man who is a known case of well controlled hypertension by angiotensin receptor type 1 (AT1-R) blockers, Osteoarthritis on non-steroidal anti-inflammatory drug (NSAID) and dyslipidemia controlled by atorvastatin 60 mg daily. The patient presented to the emergency with easy fatigability and confusion. The patient was alert and conscious. His Weight was 76 kg, Blood pressure 182/73 mmHg, Oxygen saturation 95-97% in room air. Temperature was 36.4°C. There was no neurological deficit and systemic examination was unremarkable.
Laboratory results showed blood urea 24.2 mmol/L, serum creatinine 643 µmol/L, Na 138, K 4.2 mmol/L, random blood glucose 6.1 mmol/L, total protein 59 g/L, albumin 39 g/L, alkaline phosphatase 103 U/L and ALT 63 U/L, WBCs on admission 7000, hemoglobin 10.9 g/dl, platelets 247 and 24 hours proteinuria (PU) was 1.9 g/d. Liver, thyroid function tests, ESR and C reactive protein were normal. Chest X ray and KUB were unremarkable. Renal U/S revealed normal sized echogenic kidneys with no evidence of obstruction while the small benign hyperplastic prostate was already under alpha 1 receptor blocker as a medical treatment. There was no clinical evidence of pre-renal ARF on presentation. To further clarify the nature of the ARF; glomerulnephritis screen was carried out and revealed negative (ANA, anti-ds-DNA, CRP, C3, C4, serum and urine immunoelectrophoresis, serum immunoglobulin, HCV, HbsAg). Tumor markers, CEA, Ca19-9 and PSA revealed negative. Only CK and LDH revealed 3020 and 653 U/L respectively while the other cardiac enzymes were normal. Urine showed both glomerular and non glomerular RBCs and proteinuria.
Our initial differential diagnosis was
- Interstitial nephritis due to NSAID? and/or
- Rhabdomyolysis due to atorvastatin therapy?
So the treatment was
- Stop both atrovastatin and NSAID and
- Intravenous fluids and daily laboratory follow-up
Patient showed marked improvement and discharged after 3 weeks of conservative management with: S Cr 149 µmol/L, blood urea 14.4 mmol/L, Albumin 33 g/L, CK 109 U/L and LDH 275 U/L. But 24 hour PU which was 1.9 g/d on admission went up to 15.5 g/d on discharge. Our debate concluded to discharge the patient without renal biopsy on antiproteinuric measures (AT1R blockers) and tight follow up.
Two months after discharge his S Cr went up from 149 to 266 µmol/L; 24 h PU was 11.04 g/d, both glomerular and non-glomerular haematuria, S Cholesterol 10 mmol/L, serum albumin went down to 24 g/L and patient developed moderate lower limb edema.
So renal biopsy was carried out which revealed a MPGN on a back ground of interstitial fibrosis and tubular atrophy in addition to arteriolar hypertensive changes [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5],[Figure 6]. Again after a debate the patient was discharged on a prednisolone 60 mg and cyclosphosamide on a modified dose of 1 mg/kg.
| Case Revisited|| |
Patient was followed in out patient clinic on a weekly basis for the first month then biweekly afterward. After 4 weeks of treatment patient showed initial improvement with S Cr 128 µmol/l, albumin 28 g/l, the 24 h PU 5.7 g/d (> 50% reduction) while the total cholesterol still 12.3 mmol/L as the antilipidemics were stopped due to the high creatine kinase on initial presentation. Two weeks later patient presented with severe chest infection associated with an ARF with RIFLE criteria as failure (Risk, Injury, Failure, Lost and End stage). Patient was re-hospitalized and treated with the appropriate antibiotics, while his renal function kept deteriorating. ICU admission and continuous renal replacement therapy (CRRT) was done for three days followed by intermittent dialysis through a central catheter (permicath). Once the infection subsided (2 weeks after admission) patient was discharged to continue his dialysis 3 times weekly on outpatient basis and follow up his renal profile. One week later the patient readmitted again for a venous line related sepsis. After a total of 8 weeks on dialysis from the 2nd episode of ARF and proper management, the patient discharged off dialysis with a S Cr of 300 µmol, Albumin of 27 g/L, cholesterol of 3.4 mmol/L and 24 h PU of 4.4 g/d on a combination of antiproteinuric (ACE inhibitors and AT1-R Blockers), lipid lowering drugs and antiplatelets [Table 1].
| Discussion|| |
Acute renal failure in elderly
ARF is a frequent disorder in the old population and the increased incidence of this renal syndrome in this age group is favored by some factors such as the histological and functional changes of the aged kidney, the reduced capability of this population to metabolize drugs, and their exposure to polypharmacy and to a great number of systemic diseases such as diabetes mellitus, hypertension and cardiac failure.  Among the main senile renal changes that make old people prone to acute renal failure are:
- Disturbance in the auto-regulatory vascular defense. 
- A reduction in the number of glomeruli and glomerular capillaries. 
- Their renal tubular fragility. 
- A salt and water wasting secondary to a reduced tubular reabsorption capability of these substances. 
Our patient proved to have hypertension for many years, age related osteoarthritis treated by NSAID and hyperlipidemia treated by atorvastatin. All these are independent risk factors and/or cause of ARF. His elevated serum level of CK and LDH at presentation raised the question of associated drugs related rhabdomyolysis especially with atorvastatin.
The patient presented to the emergency with complaints of easy fatigability and confusion without any nephrological symptoms. Atypical presentations of the ARF in elderly have been clearly reported. ,,, In the elderly, the diseases usually have patterns of presentation different to the ones observed in the young population (paucisyntomatic). Signs and symptoms are frequently less defined in the age population. Moreover, any disease could appear merely as one of the entities known as the geriatrics giants: confusional syndrome, falls, immobility syndrome and acute urinary or fecal incontinence. These presentation patterns are called "atypical" but actually they are "typical" in this population. ,,,
In additions, due to the convinced influence of the senile tubular frailty and tubular dysfunction, in old people is frequently observed the so called "intermediate syndrome", it means a patient suffering from a pre-renal acute renal failure who seems to be suffering from a parenchymal one since this old patient usually has not only high plasma urea and creatinine but also urinary indices compatible with acute tubular necrosis. However, they resolve the renal failure with volume expansion as a pre-renal insufficiency does. However, while the classical pre-renal failure recovers in 24-48 hours of rehydration, the intermediate syndrome does it in a longer period. 
Acute renal failure as a complication of nephrotic syndrome
ARF is a known complication of patient with nephrotic syndrome mostly with minimal change disease (MCD) 5% of cases, while focal segmental glomerulosclerosis (FSGS) only represent 8% of cases specially the collapsing FSGS which usually associate the HIV disease. Membranous nephropathy is rarely complicated by ARF while diabetic nephropathy and amylodosis is very unusual. An increased risk noted in males, older individuals, and those with hypertension, lower serum albumin levels and greater proteinuria.
However, ARF usually happen as a complication of nephrotic syndrome or its treatment. It is quite uncommon that the first presentation, as in our case, of nephrotic and nephritic syndrome mainly membrano proliferative GN to be ARF. ,
The outcome is generally not so good in patients with apparently idiopathic MPGN. Up to 50-60 % of untreated patients will progress to ESRD within 10-15 yrs. 25-40 % will maintain apparently normal renal function. Spontaneous improvement occurs in < 10 % of cases. Bad prognostic signs at presentation include:
- The nephrotic syndrome.
- Renal insufficiency.
- On renal biopsy, crescents, tubulointers titial disease (interstitial infiltration and fibrosis, tubular atrophy).
The risk of progression usually correlates more closely with the severity of the tubulointerstitial injury than with the degree of glomerular damage. The long-term prognosis tends to be relatively good in patients who present with asymptomatic hematuria and proteinuria and who have focal, rather than diffuse, glomerular involvement on renal biopsy. ,,,,,, Our patient despite he presented with ARF, he has both hematuria and proteinuria without casts. As his renal function improved, his proteinuria dramatically increased with the appearance of the cardinal manifestation of glomerular disease which proved to be MPGN on renal biopsy.
Immunosuppressive therapy in elderly
Immunosenescence describes an increasingly insufficient function of the immune system that increases the susceptibility of the elderly toward infection, autoimmune disease, and cancer, contributing significantly to morbidity and mortality. , The immune system undergoes a complex and continuous remodeling as a result of aging. Both volume and mass of virtually all solid lymphoid organs become smaller. These changes are paralleled by age-related morphologic changes of the immune system (blurring of histologic architecture, fatty infiltration, fibrosis, and reduction of germinal centers) in addition to functional alterations. 
These age-related changes result in both quantitative and qualitative modifications with increased, decreased, and unchanged functions of specific subsystems, rather than a global deterioration of the immune system as previously believed. , The most striking alterations are found in phenotypes and functions of T-cell components and less frequently in components of the natural (innate) immune system. Consequently, chemotaxis, phagocytosis, natural cytotoxicity, and complement activity are relatively well preserved in elderly individuals.  Alterations of B cells seem to be secondary to T-cell dysfunction. 
A greater degree of immunosuppression (IS) results in an increased risk of infectious complications in all patients (young and old). However, as previously mentioned, immunocompetence decreases with age; as a result, older individuals are more susceptible to infectious complications at lower levels of immunosuppressive therapy. In addition, increased incidence of associated co-morbidities and altered pharmacokinetics make prescribing immunosuppressive medications in the elderly a very challenging issue. Consequently, modifications of the immune system because of aging may request an age-adapted immunosuppression in parallel with close patient monitoring. 
After a debate about using the standard immunosuppressive treatment in MPGN in elderly above 80 yrs of age; patient received steroid and modified dose of cyclophosphamide. After initial improvement defined as more than 50 % reduction in the PU, increased serum albumin and improvement of kidney function. Patients develop two subsequent episodes of septicemia with ARF. After stoppage of IS, patient needed to be hospitalized for a total of three weeks. So, the benefit of using IS in old man was counteracted by the infectious complications that lead to ARF and long time hospitalization. So, the question is: is there is a place to use aggressive IS in elderly above the age of 80ys.
| Conclusion|| |
MPGN can present initially as ARF. Is it wise to start an aggressive IS therapy in elderly patient above 80 yrs old even in a modified doses. Is there any standardization regarding the dose and type which guide the use of IS in elderly.
Further prospective studies are necessary to address this issue.
| Questions and Answers|| |
Dr. Akram Askar (King Khaled University Hospital, Chairman of the RNTC): the presentation is now open for discussion.
Dr. Mohammad Ziad Souqiyyeh (SCOT): When somebody present with proteinuria usually above the age of 40 years, we do urine immuno electropheresis, just to see if the patient has multiple myeloma. Was that done?
Speaker: Yes. Actually the patient presented as ARF with creatinine over 600 umol/L, without any previous medical record, and during initial investigation the proteinuria was 1.9 g/24 hrs. and in our differential diagnosis we consider the acute interstitial nephritis because of the history of non-steroidal antiinflammatory drugs for long period with long standing hypertension and he is receiving anti-lipid drugs, so all these together give the picture of systemic disease affecting the kidneys.
Dr. Souqiyyeh: But later on, he presented with heavy proteinuria and my question is why the renal biopsy was not done at the first presentation?
Speaker: Your point is valid, for any patient presented with proteinuria, but here the scenario is different that our patient is over 80 years old presented with ARF, can be due to interstitial nephritis, and we give him the chance to recover his renal function, and the most interesting that once his renal function was restored, the proteinuria increased to as 15 g/24 hrs, and here we did the biopsy, with the debate of to do biopsy or not? And to treat the patient or not?
Dr. Souqiyyeh: My last comment on immunosuppressive therapy, usually in younger patient with such finding, we apply full regimen of immunosuppressive drugs; here in this case what was your therapeutic plan?
Speaker: We gave the patient 50 mg of cyclophospamide (1/2 of the usual dose) plus 60 mg of steroids daily, during this course patient developed a second attack of ARF mostly precipitated by sepsis, which indicated starting the dialysis therapy.
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Department of Nephrology, Riyadh Armed Forces Hospital, Riyadh
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
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