Epidemiologic Trend Changes in Acute Renal Failure—A Tertiary Center Experience from South India

Abstract

Background. There are little data on the incidence of acute renal failure (ARF) from India due to the absence of central registry. The etiology, course, and outcome of ARF differ in various parts of India. Significant trend changes were reported even within a same center over a period of time. Aim. To find out the epidemiologic trend changes in ARF patients, the authors compared the profile of patients admitted by the Department of Nephrology from 1995–2004 with previously published data from 1987–1991. Methods. Data collected from case records of patients admitted with ARF were systemically analyzed for age, gender, etiology, course, and outcome. A total of 32 variables were collected per person retrospectively. The chi-square test, Fisher's exact test, and student t-test were used as tests of significance (p< 0.05 was taken as statistically significant). Results. A total of 1112 patients were diagnosed to have ARF from 1995–2004. The mean age was 37.08 ± 3.4 yrs. There were 669 (60.1%) males. Medical, obstetric, and surgical causes accounted for 87.6, 8.9, and 3.4 percent of ARF, respectively. Among the medical causes of ARF, acute diarrheal disease was the most common. Other causes of medical ARF included drugs, glomerulonephritis, sepsis, snake bite, leptospirosis, malaria, and copper sulphate, which accounted for 13.4, 9.3, 8.8, 7.8, 7.5, 4.4, and 4.3 percent, respectively. In comparison with the data from 1987–1991, medical ARF remained the most common cause of ARF, though without any statistical significance (87.6 percent vs 89.5 percent, p>0.32). Though surgical ARF had more than doubled from 1.5 percent from 1987–1991 to 3.4 percent (p<0.01) during the present study, it is much less when compared to similar studies in the literature. Obstetric renal failure more or less remained the same (8.9 percent vs 9 percent, p>0.4). A statistically significant decline was noted in overall as well as individual group mortality. The overall mortality declined from 26.4 percent to 19.6 percent (p<0.02). Regarding the outcome of ARF, 611 patients (54.94 percent) showed a total recovery, a partial recovery was noted in 192 patients (17.26 percent), and 91 patients (8.18 percent) had persistent dialysis-dependent renal failure. The factors noted to occur more frequently in the deceased were high entry serum creatinine (>440 μmol), jaundice, sepsis, oliguria, anemia, hypoalbuminemia, and hospital-acquired ARF. The overall requirement of dialysis was 69.0 percent. Hemodialysis was the most common modality of renal replacement therapy. Conclusions. ARF in South India differs in some important aspects when compared with data from other parts of the country. Significant trend changes were noted with time even within our center. Acute diarrheal disease was the most common cause of ARF. Leptospiral ARF was on the decline, and drugs, sepsis, and malaria were the emerging ARF causes. The incidence of surgical ARF was on the rise. Despite improvements in antenatal care, obstetric renal failure remained a significant cause of ARF. Hemodialysis became the preferred mode of renal replacement therapy.

Keywords:

• acute renal failure
• epidemiology
• medical
• surgical
• obstetric

INTRODUCTION

Acute renal failure (ARF) is characterized by an abrupt deterioration of renal function over a period of hours to days, resulting in the failure of the kidney to excrete nitrogenous waste products and maintain the fluid and electrolyte homeostasis.[1] The acute deterioration of renal function remains a common complication of many non-renal medical problems and therapies requiring hospital admission.[2]

There are very limited data on the overall epidemiology of ARF. It is crucial to know the incidence, etiology, and clinical features of ARF to promote prevention strategies and implement adequate resources for the management of this entity.[3]

Despite advances in renal replacement therapy, the mortality in ARF remained more or less same in the last five decades. Several factors might contribute to this persistent high mortality, such as a more elderly population with ARF and the fact that those with more severe illnesses survive long enough to develop renal failure.[4] Recent data have shown that even small changes in renal function are associated with a substantial increase in mortality.[4],[5]

The frequency of ARF varies greatly depending on the clinical setting. For example, the frequency among patients is 1 percent at admission to the hospital, 2 to 5 percent during hospitalization, and as high as 4 to 15 percent after cardiopulmonary bypass.[6]

Although reliable statistics on the prevalence of ARF among different tropical countries are not available, statistics based on a referral to a dialysis unit suggest that the condition is more common among the tropics.[7]

The etiological spectrum of ARF is markedly different between developed and developing countries. It is closely linked to environmental and socioeconomic conditions. Surgery, trauma, and sepsis are the most common causes of ARF in developed countries whereas in developing countries, diarrheal diseases and tropical diseases still predominate. ARF due to obstetric causes almost disappeared from western literature but remain a significant part in developing world.[8]

The etiology, course, and outcome of ARF differ in various parts of India.[9–11] Studies from North India, for example, reported a low incidence of post-diarrheal ARF.[11],[12] ARF due to intravascular hemolysis induced by drugs or infection in association with G6PD deficiency was an important cause of ARF in North India[11] but rarely reported from other Indian centers.[9],[10] Leptospiral ARF was not at all reported in an Eastern Indian study.[9] Significant trend changes were reported even within the same centre over period of time.[12]

Understanding the changing spectrum of ARF is necessary to facilitate quality improvement efforts for health care providers and prioritize their efforts so as to design successful interventional trials.[12]

The aim of the present study is to identify the etiologies, their trends with time, and the outcomes of ARF from a single tertiary center in South India.

METHODS

This is a single-center, retrospective study. The data for this purpose were collected from the case records of the Department of Nephrology at the Tamilnadu Dr. MGR. Medical University. In all, 1112 patients admitted with ARF between 1995–2004 were included in the study. ARF was defined as acute reduction in renal function with more than a 2 mg rise in serum creatinine in the presence of normal sized kidneys. Patients with preexisting renal disease, diabetes, and hypertension were excluded from the study.

The diagnosis was based on history, physical examination, laboratory values, and clinical course. All patients were subjected to urine analysis, hemogram, blood biochemistry (which included urea, creatinine, electrolytes, uric acid, calcium, and phosphorus), and ultrasound abdomen. Renal biopsy was done in selected cases with unexplained renal failure, a duration of renal failure of more than four weeks, and in those with features suggestive of glomerular disease.

Oliguric renal failure was defined as urine output <400 mL/24hrs. Hospital-acquired renal failure was defined as renal failure that developed during hospitalization for non-renal problems in patients whose serum creatinine was normal at admission. Community-acquired ARF was defined as renal failure developing outside the hospital. These patients were dialyzed whenever they developed specific indications. A total of 32 variables were collected per person for analysis. Regarding the outcome, ARF recovery was defined as the normalization of serum creatinine within 12 weeks. Partial recovery was defined as persistent dialysis-independent renal failure.

These data (1995–2004) were compared with our previously published data (1987–1991)[13] from the same center to find out any significant trend changes.

Statistical Analysis

The data were systematically analyzed using SPSS 10.0 version. The results were expressed as mean ± SD. The chi-square test, Fisher's exact test, and student t-test were used as tests of significance; p< 0.05 was taken as statistically significant.

RESULTS

A total of 1112 patients were admitted with a diagnosis of ARF from 1995–2004. There were 669 males (60.1 percent) with a mean age of 37.08 ± 3.4 yrs. Medical causes were the most common cause of ARF (87.6 percent), followed by obstetric (8.9 percent) and surgical (3.4 percent) causes.

Among the medical causes of ARF, acute diarrheal disease was predominant. Other etiologies of medical ARF included drugs (13.4 percent), glomerulonephritis (9.3 percent), sepsis (8.8 percent), snake bite (7.8 percent), leptospirosis (7.5 percent), malaria (4.2 percent), and copper sulfate poisoning (4.7 percent). The entire spectrum of ARF from 1995–2004 is given in Table 1.

Table 1 Spectrum of ARF, 1995–2004

	Diarrheal disease	Snake bite	Malaria	Sepsis	Glomeruolonephritis	Drugs	Coppersulfate	Leptospirosis	Others	Surgical	Obstetric
Percentage of ARF	28.6	7.8	4.4	8.8	9.3	13.4	4.3	7.5	3.2	3.4	8.9
Dialysis need %	66.1	94.2	77.5	78.5	84.6	44.6	64.5	53.5	55.5	63.1	85.8
Mean age ±SD	41.82 ± 3.86	35.6 ± 4.12	35.25 ± 4.36	48.7 ± 3.62	32.42 ± 1.28	40.6 ± 5.2	28.32 ± 2.66	40.48 ± 3.74	37.26 ± 4.26	46.28 ± 2.68	21.13 ± 1.62
Sex (M/F)	1.82	2.22	2.26	1.51	2.05	1.5	7.0	2.5	1.76	1.92	—
Mortality %	8.7	27.5	26.5	56.1	21.1	6.6	35.4	9.5	13.8	47.3	18.1
Peritoneal dialysis %	39.3	18.2	57.8	55.8	9.0	47.7	38.7	46.6	40	29.1	17
Hemodialysis %	60.6	81.7	42.1	38.9	90.9	52.2	61.2	48.8	60	70.8	80.8

Pregnancy-related ARF occurred in 8.9 percent of patients, of which preeclampsia accounted for 43.3 percent, followed by antepartum hemorrhage in 25.3 percent of cases. Less common causes of obstetric ARF were septic abortion and post-partum hemorrhage.

Surgical ARF accounted for 3.4 percent of ARF, of which post-cardiac surgery was the most common, followed by gastrointestinal and urological surgeries.

When compared with the previous data, acute diarrheal disease continued to account for one-third of ARF. A dramatic decline in leptospiral ARF was noted, from 31 percent to 7.5 percent. The other significant trend changes were given in Table 2. ARF due to drugs, snake bite, and post-operative ARF were statistically shown to be increased. Obstetric ARF, ARF due to copper sulfate, and glomerulonephritis-related ARF remained the same.

Table 2 Comparison of ARF

	1987–1991	1995–2004	p value
Medical	348 (89.5%)	975 (87.6%)	NS
Diarrheal disease	118 (30.5%)	319 (28.6%)	NS
Drugs	21 (5.4%)	150 (13.4%)	0.003
Glomerulonephritis	33 (8.5%)	104 (9.3%)	NS
Leptospirosis	120 (31%)	84 (7.5%)	0.012
Snake bite	18 (4.7%)	87 (7.8%)	0.032
Obstetric	17 (9%)	99 (8.9%)	NS
Surgical	6 (1.5%)	38 (3.4%)	0.004
Total	387	1112

In all, 69.0 percent required dialytic support, of which 64.3 percent were treated by hemodialysis and 34.6 percent by peritoneal dialysis. Eight patients were treated by continuous venovenous hemofiltration (CVVH). The management data are given in Table 3. High entry serum creatinine (>440 μmol), jaundice, sepsis, oliguria, anemia, and hypoalbuminemia were noted to have occurred more frequently in the deceased. The predictive factors of mortality were given in Table 4.

Table 3 Management of ARF

	1987–1991	1995–2004
Conservative	99 (25.6%)	344 (30.9%)
Dialysis	288 (74.4%)	768 (69.0%)
Peritoneal dialysis	195 (67.7%)	266 (34.6%)
Hemodialysis	93 (32.3%)	494 (64.3%)
Continuous renal replacement rherapy	—	8 (1.04%)
Mortality	104 (26.4%)	218 (19.6%)

Table 4 Risk factors for mortality

	Survivors	Deceased	p value
Mean age ± SD	32.34 ± 2.78	38 ± 4.18	NS
Sex (M/F)	1.52	1.41	NS
% oliguric ARF	76.7%	91.6%	<0.02
Sepsis	77.2%	31.8%	<0.02
Mean Hb	8.68 ± 4.2	6.02 ± 0.14	<0.05
Entry Cr>5mg	38.81%	61.2%	<0.05
Serum albumin <3mg	31.8%	68.16%	<0.001
Jaundice	23.12%	54.4%	<0.05

Regarding the outcome of ARF, the overall mortality was 19.6 percent. The median follow-up was 12 weeks (2–46 weeks). As many as 11 percent of patients were lost to follow-up after discharge. All told, 611 patients (54.94 percent) had a total recovery, partial recovery was noted in 192 patients (17.26 percent), and 91 patients (8.18 percent) became dialysis-dependent.

When patients were divided into community- or hospital-acquired ARF, the latter developed in 7.9 percent of cases. It was most often multifactorial in origin, and most had sepsis or drugs as an etiology. The overall prognosis of hospital-acquired ARF was poor (56.8 percent mortality), and the requirement of dialysis was also high (84 percent). The salient differences between hospital- and community-acquired ARF are given in Table 5.

Table 5 Comparison of hospital- and community-acquired ARF

	Hospital-acquired ARF	Community-acquired ARF	p value
Percentage of ARF	7.9	92.08	0.001
Mortality	56.8%	16.4%	0.03
Dialysis requirement	84%	67.7%	0.012
Mean age ± SD	38.16 ± 4.2	34.82 ± 2.6	NS
Sex ratio	1.25	1.11	NS
Recovery	43.1%	74.5%	0.024

DISCUSSION

The number of admissions due to ARF remained stable in the last decade. It accounted for 4.1% of admissions in this department from 1987–1991 and 3.8% from 1995–2004 (p=0.32). As with the data from other centers in India,[9],[10] the most common cause of ARF remained medical. Of the medical causes, acute diarrheal disease was the leading cause of ARF, the prevalence of which was more or less the same (p=0.26) despite an improvement in living conditions and a greater emphasis on aggressive rehydration. This may be in part due to a lack of awareness on the part of general practitioners, delays in correction of fluid electrolyte losses, and late referral.[9] Although there seems to be a decline in ARF due to diarrheal disease reported from other centers,[12] such a pattern was not observed here.

Drugs became the second most common cause of ARF. Unknown analgesic combinations was the most common reason for admission due to drug-induced ARF, followed by Rifampin and NSAIDS. This may be due to the excessive use of over-the-counter drugs. Rifampin-induced ARF was noted to occur frequently in patients who received intermittent therapy.[14]

It is obvious that there has been a dramatic decline in the incidence of leptospiral ARF. This zoonotic disease, which was once the most common cause of ARF in this part of the world,[13] showed a statistically significant downward trend. Whether this reduced incidence is real or due to greater awareness, better diagnostic facilities, and/or the widespread use of empiric penicillin is not clear. Only a long-term epidemiologic study can answer this question.

ARF following snake bite is a common problem even today in rural India,[13] contributing to 7.8 percent of ARF cases. As the study occurs in a tertiary referral center, most patients were referred late with renal failure, which is evident from the fact that 94.2 percent of patients with snake bite-induced ARF required dialysis. Of these, 74.8 percent had evidence of disseminated intravascular coagulation. The incidence of ARF due to snake bite almost doubled from 4.7 percent to 7.8 percent, the reason for which again likely being a lack of awareness and prompt referral.

In the last decade, malaria has returned to many places from where it is said to have been eradicated. ARF due to falciparum malaria has been reported mostly from Southeast Asia and Africa.[15] Malarial ARF constituted 4.4 percent of ARF, mostly (93.8%) due to plasmodium falciparum. Plasmodium vivax was also observed in 6.2 percent of malarial ARF, a finding similar to that of other investigators.[16] Malarial ARF was not reported in the current authors' previous study.[13]

Sepsis is the emerging cause of ARF. As with malaria, this subset of ARF was also not reported in the previous study[13] and accounted for 8.8 percent of ARF. Sepsis- induced ARF was among the worst prognostic group, which showed a 55 percent mortality rate and most often had multiorgan failure and significant comorbidities.

Among glomerular diseases, crescentic glomerulonephritis, followed by post-infectious proliferative glomerulonephritis, systemic lupus erythematosus, and IgA nephropathy (in order of frequency), accounted for 9.3 percent of ARF. The incidence of post-infectious glomerulonephritis remained more or less the same.

Copper sulfate ingested with suicidal intent was reported as a cause of ARF only from India.[9] The incidence of ARF due to copper sulfate ingestion increased from 3.4 percent in 1987–1991 to 4.3 percent in 1995–2004, showing still now that it remains a popular means of committing suicide, especially among males.

Other causes of medical ARF include radiocontrast (1.07%), myeloma (0.89%), post-chemotherapy (0.44%), and rhabdomyolysis (0.62%). The rarity of these causes reflects the fact that only patients with severe renal failure requiring nephrologic intervention were shifted to nephrology ward.

Obstetric renal failure continues to remain an important cause of ARF in India,[9] unlike the experiences of the more developed world. This could have resulted from a rise in the number of obstetrical patients in the referral units and better awareness among treating physicians. ARF due to septic abortions declined significantly. The reasons for such observation may be the legalization of the termination of pregnancy. Pre-eclampsia-related ARF is on the rise; in fact, this is the most common cause of obstetric ARF in the present study (in contrast to ARF due to septic abortion, which was the most common in the previous study[13]). Whether this is due to improved detection or a real increase in prevalence is not known.

The surgical ARF in this series included only post-operative patients with severe renal failure requiring nephrologic intervention. Cardiothoracic surgeries resulted in more post-operative renal failures, followed by gastrointestinal and urologic surgeries. The possible reasons for the above-mentioned observation may be wider patient inclusion (older age, comorbidities) and the use of complex procedures. Patients with obstructive nephropathy were not included in the study. The reasons for a low surgical ARF in our cohort was discussed in detail elsewhere.[10]

Mortality rates in ARF range from approximately 7 percent among patients admitted to a hospital with prerenal azotemia to more than 80 percent among patients with postoperative ARF.[6] Despite major advances in dialysis and intensive care, the mortality rate among patients with ARF requiring dialysis had not decreased appreciably over the past 50 years.[5] This may be explained by two demographic changes: the age of patients continuing to rise and coexisting serious illnesses were increasingly common among these patients. With the advent of dialysis, the most common causes of death were sepsis, cardiopulmonary dysfunction, and the withdrawal of life-support measures.[6]

Mortality in patients with ARF were known to be high with coma, assisted respiration, hypotension, jaundice, prolonged renal failure, high entry serum creatinine, hypoalbuminemia, anemia, sepsis, severe comorbidities, multiorgan failure, and oliguria.[3] In this study, oliguria, high entry serum creatinine (>440 μmol), jaundice, sepsis, anemia, and hypoalbuminemia were found to be risk factors associated with mortality (see Table 4).

Patients with nonoliguric ARF had a better prognosis than those with oliguric renal failure, probably due in large measure to the decreased severity of the insult and the fact that many had drug-associated nephrotoxicity or interstitial nephritis.[6]

The percentage of patients with acute renal failure who required dialysis was 69 percent. Of the dialysis modalities, hemodialysis was the most commonly used modality, as compared to the authors' previously published study, wherein peritoneal dialysis was used more. [13] The wider application of hemodialysis resulted in part from a change in the policy decision-making of the unit. Previously, most ARF patients were treated by peritoneal dialysis; now, patients are taken up for hemodialysis only if they are hemodynamically stable. Among the subgroup of patients who survive initial dialysis, only 8.18 percent required long-term dialysis, demonstrating the potential reversibility of the syndrome.

The low mortality in these patients may be in part due to case mix. This cohort had a younger age, a greater frequency of ARF due to medical causes, predominantly community-acquired ARF, and less frequent multiorgan failure accounting for the observed reduction in mortality.

The present study had a few potential limitations. This was a retrospective study, wherein data were collected from department registry without blinded reviewers and hence were subject to information bias. Moreover, this is a single-center study, and the generalizability of these findings is limited.

This study attempted to identify the risk factors associated with mortality. However, because it is retrospective and in part due to case mix, the relative importance of each risk factor could not be identified. There is a need for a prospective multicenter national study to identify the risk factors associated with poor prognosis so that risk stratification can be done.

CONCLUSIONS

ARF in South India differs in some important aspects when compared with data from other parts of country. Significant trend changes were noted with time even within our center.

Acute diarrheal disease was the most common cause of ARF. Leptospiral ARF was on the decline, and drugs, sepsis, and malaria were the emerging causes. The incidence of surgical ARF was also on the rise. Obstetric renal failure despite improvements in antenatal care remains a significant cause of ARF. Hemodialysis became the preferred mode of renal replacement therapy.