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Laboratory tests that may be done include: levels, aggressive blood pressure control, angiotensin II inhibition, and dietary protein restriction. Additional therapeutic targets include microalbuminuria and macroproteinuria. An The levels of these tests will increase as kidney approach to each of these parameters is discussed damage gets worse. Other laboratory tests that 1. Tight blood glucose control
The DCCT (Diabetes Control and Complications Trial) demonstrated the importance of tight blood glucose control in slowing the development of proteinuria in Type 1 diabetics. In this regard, patients randomized to tight glucose control (HbA1C levels < 6.5%) versus regular control (8- A kidney biopsy confirms the diagnosis. However, 9%), demonstrated 39 and 54% lower rates of clinical diagnosis can be done without a biopsy if the following three conditions are met with: macroalbuminuria, respectively, over the two years of the trial.
Similarly the UKPDS(United Kingdom Prospective Diabetes Study) in Type II diabetes showed a 25% 3. No other kidney or renal tract disease risk reduction in microvascular complication in A biopsy may be done, however, if there is any 2. Blood pressure control
Diabetics with heavy proteinuria, but lacking the Hypertension in diabetic patient may be due to disease for a sufficient period of time and/or coexisting “essential” hypertension, or due to retinopathy, may require renal biopsy. These myriad of other secondary causes, such as renal p a t i e n t s m a y s u f f e r f r o m p r i m a r y vascular disease. Isolated systolic hypertension has been attributed to the loss of elastic nephropathy, or other glomerular diseases.
compliance of atherosclerotic large vessels. Both Diabetic glomerulopathy is the most common systolic and diastolic hypertension markedly cause of nephrotic syndrome. Thus, early in the course of the disease, the serum creatinine is nephropathy and aggressive antihypertensive normal despite heavy proteinuria (> 3 grams/24 management is able to greatly decrease the rate hours). In this regard, a diabetic patient of fall of GFR. Appropriate antihypertensive presenting with elevated serum creatinine in the intervention can significantly reduce mortality absence of macroscopic proteinuria should from 94 to 45% and a reduction in the need for suggest additional diagnostic possibilities (such as dialysis and transplantation from 73 to 31% 16 other glomerulopathies) . The diagnostic utility of years after development of overt nephropathy. proteinuria is less useful in patients treated with Choice of antihypertensive therapy:-
angiotensin converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs), since both classes of drugs are known to reduce Use of ACEI and ARBs as these may lead to hyperkalemia in patients of advanced renal MEDICAL THERAPY OF DIABETIC NEPHROPATHY :
The medical therapy of diabetic glomerulo- ACEI are contraindicated in bilateral renal sclerosis includes strict control of blood glucose macroproteinuria and renal failure. American Targets for blood pressure control:-
Diabetic Association (ADA) guidelines suggest assessing for microalbuminuria (normal < 30 • <130/80 mm hg in absence of proteinuria mg/24 hours or less 30 mcg/mg creatinine for • <125/75 mm hg in presence of proteinuria.
a spot urine collection) at the time of diagnosis 3. Angiotensin II inhibition : The ACE inhibitor
in all type 2 diabetics, in all type I diabetics with trial in diabetic nephropathy was the first disease duration > 5 yrs, and annually randomized, placebo controlled trial that showed the beneficial effect of ACE inhibitors aggressive therapy of microalbuminuria, taken i n t h e t r e a t m e n t o f d i a b e t i c along with angiotensin II inhibition, is glomerulosclerosis. Subsequent studies have expected to slow disease progression.
6. Macroproteinuria
Heavy proteinuria is a risk factor for progressive a re f i rs t l i n e t h e ra p y fo r d i a b e t i c renal failure, 16 including diabetic nephropathy. glomerulosclerosis, but ARBs are regarded by There is abundant evidence that abrogating some as equivalent. The beneficial effect of proteinuria with dietary and antihypertensive angiotensin II inhibition may result from: interventions, and/or ACE inhibitors, 1 and/or a) a decline in glomerular hypertension (with proteinuric states. In this regard, combination therapy with both ACE inhibitors and ARBs may provide benefit over ACE inhibitors alone. Finally, nephrotic diabetics treated with ACE inhibition, and exhibiting a reduction in c) a decrease in angiotensin II stimulated proteinuria to < 1 gm / day, demonstrated stable renal function for up to 8 to 15 years. Taken 4. Dietary protein restriction : In some reports,
together, therapeutic measures directed at dietary protein restriction has been shown to reducing macroscopic proteinuria would be slow the loss of GFR in proteinuric diabetics, expected to slow the progression of diabetic although the data are not conclusive. Protein nephropathy, and angiotensin II inhibition is the restricted diets (0.6-0.8 g/kg body wt/day) mainstay of therapy for attaining that goal.
Other aspects of treatment : Treatment of
progressive renal disease includes prevention of proteinuria, and glomerulo-sclerosis, and renal osteodystrophy with sodium and phosphate restriction and use of phosphate binders, treatment and prevention of anaemia etc.
5. Microalbuminuria : Microalbuminuria
Avoidance of nephrotoxic drugs in proteinuric diabetic patients will prevent form onset of acute proteinuria. Macroscopic proteinuria is a major risk factor for progression to ESRD, thus measures to reverse microalbuminuria may Radiocontrast media are nephrotoxic in diabetic retard development of clinical nephropathy. nephropathy and careful hydration is mandatory Patients with microalbuminuria treated with SPECIAL CONSIDERATIONS
Survival analysis shows the two modalities are Insulin metabolism in CKD : Unutilized insulin is
comparable with regard to patient outcome. excreted by kidney normally which accumulates However, when compared to non-diabetics, diabetic patients on dialysis do substantially in CKD. So if we fail to reduce insulin dose as worse, with five-year survival rates as low as 5% kidney disease progresses, patients will for elderly type 2 diabetics. With meticulous experience hypoglycaemia. So reducing insulin management, others have shown three-year dose and switching to short acting insulin survival rates as high as 58%. .The reasons for analogues is recommended in this situation. It is poor survival rates relate to the high incidence of recommended to avoid long acting Insulins in CKD preexisting cardiovascular disease, late referral both for predialysis care, as well as vascular access Oral antidiabetic drug: 97% of the most
placement, malnutrition, and co-existing vascular commonly used oral antidiabetic drug Metformin problems (in particular, peripheral vascular is excreted by normal kidney within 12 hrs. In CKD disease with associated ischemic toes and feet). it will accumulate and lead to lactic acidosis, a Furthermore, diabetes and smoking have been shown to be significant risk factors for So metformin should be stopped when the eGFR is atherosclerotic heart disease in dialysis patients, <35 ml/mt/1.73 m correlates to serum creatinine similar to what is seen in the general population. o f a p p r o x m i m a t e l y 1 . 7 m g / d l . O l d e r The anemia of chronic renal disease may further sulfonylurea(SU) are excreted mainly through complicate the course of patients with significant kidney. Only 10% of second line SU are excreted by coronary artery disease. Taken together, these kidney but are long acting and may accumulate in data suggest that the survival of diabetic patients CKD, so we must be cautious while using these. Meglitinides and Thiazolidinediones are not aggressive attention to risk factors for c a rd i o va s c u l a r d i s e a s e ( hy p e r te n s i o n , dyslipidemia, smoking, etc.), awareness and therapy of diabetic foot problems, and early Monitoring glycaemic control in CKD : As kidney
nephrology referral (as GFR falls or with disease develops, the turnover of red blood cells progressive proteinuria) for vascular access becomes abnormal. Usually there is prolonged life span of RBCs, perhaps because the person is anaemic. So hemoglobin has more time to 2. Peritoneal dialysis : The second option for renal
become glycated. In such conditions HbA1 replacement therapy in diabetic patients with kidney disease may be falsely high. Hb may also be ESRD, is peritoneal dialysis. When compared to carbamylated with some of the waste products, hemodialysis, fewer patients are treated with peritoneal dialysis. Patients opting for peritoneal dialysis tend to be healthier and more involved in compounds will interfere with the measurement their medical care. While no clear survival of HbA1c. This is one more reason for HbA1 cto be advantage for peritoneal or hemodialysis has falsely high. Correction of anaemia may lead to been demonstrated, patients treated with peritoneal dialysis may experience labile blood Renal replacement therapy:
glucose levels (attributed to the high glucose 1. Hemodialysis : Hemodialysis and peritoneal
concentrations inherent to PD dialysate) and dialysis are the two forms of dialysis used to treat increased risk of malnutrition (secondary to diabetic patients with end stage renal disease. excessive protein losses in dialysate effluent).
3. Transplantation : By far the best treatment for
ESRD from diabetes is kidney transplantation. The rising incidence of diabetes means that Kidney transplantation in diabetics with end-stage clinicians can expect to find an increased rate of renal disease may include kidney transplantation diabetic nephropathy, and increasing numbers of a l o n e , o r c o m b i n e d k i d n e y - p a n c r e a s patients requiring renal replacement therapy. transplantation. The former treats renal failure, Understanding the natural history of diabetic the latter both renal failure and diabetes. Patient nephropathy, the early recognition of diabetic survival following kidney transplantation without complications, and timely initiation of therapy to a pancreas has consistently been demonstrated to slow progression are cornerstones in the be superior to any form of dialysis. Data from the management of this condition. Aggressive Organ Procurement and Transplantation Network treatment of hyperglycemia and hypertension, reported one-, three-, and five-year patient the use of angiotensin II inhibitors, and timely survival rates for transplanted diabetics of 90, 79 therapy of micro and macroproteinuria are and 66%, respectively. This compares to a two essential features of optimal therapy. For patients year survival rate in diabetic patients on hemodialysis of 58%. The improved survival of replacement options include dialysis and kidney renal transplant patients over those treated with transplantation, with transplantation conferring a hemodialysis must be interpreted in light of the fact that they are selected for transplantation, References:
whereas patients with extensive co-morbidities 1. Strojek K et al, Nephropathyof type 2 tend to remain on dialysis. Living donor diabetes: Evidence for hereditary factor. transplants confer an allograft survival advantage over cadaveric donors, with three-year allograft 2. Hostetter T, Rennke H, Brenner B. The case survival rates of 88 and 78% for living and cadaveric donor transplants, respectively. initiation and progression of diabetic and However, both modalities are superior to dialysis with three year patient survival rates of a p p r o x i m a t e l y 8 8 - 9 4 % .
transplantation is renal transplantation that is performed prior to instituting dialysis. Preemptive receptors in the pathogenesis of diabetic transplantation may confer a survival advantage nephropathy. Kidney Int . 1997; 52:S7-S11.
that is superior to transplanting patients on 4. Brownlee M. Biochemistry and molecular dialysis. In this regard, the time spent on dialysis prior to transplantation portends worse survival rates for patients. For example, in patients on 5. Parving H, Smidt U, Andersen A, Svendsen dialysis < 6 months, 12-24 months, or >48 months had mortality rates of 21%, 41%, and 72%, kidney function in diabetic nephropathy. survival was seen in cadaveric transplants performed in patients receiving hemodialysis for more than two years prior to the transplant. In those studies, the allograft survival rate was only 7. Anjali, Jacob J J, Nephropathy in Diabetes; 8. Carstens S, Hebert L, Garancis J, Piering W, 17. Zeller K, Whittaker E, Sullivan L, et al. Effect diabetic glomerulosclerosis: recognition progression of renal failure in patients with insulin-dependent diabetes mellitus.
9. Brenner BM. Regarding: “Management of 18. Klahr S, Levey AS, Beck GJ, et al. The effects glomerular proteinuria: a commentary.” J of dietary protein restriction and blood- chronic renal disease. Modification of Diet 10. Lewis E, Hunsicker L, Bain R, Rohde R. The inhibition in diabetic nephropathy. N Engl J 19. Molitch ME, DeFronzo RA, Franz MJ, et al. 11. Lewis EJ, Lewis JB. ACE inhibitors versus angiotensin receptor blockers in diabetic nephropathy: is there a winner? J Am Soc 20. Breyer JA, Bain RP, Evans JK, et al. 12. Hostetter T. Prevention of end-stage renal disease due to type 2 diabetes. N Engl J 13. Zatz R, Bunn B, Meyer T, Anderson S, The Collaborative Study Group. Kidney Int. o f d i a b e t i c g l o m e r u l o p a t h y b y 21. Peterson JC, Adler S, Burkart JM, et al. p h a r m a co l o g i ca l a m e l i o rat i o n o f Blood pressure control, proteinuria, and 14. Wilmer WA, Rovin BH, Hebert CJ, Rao SV, Ann Intern Med. 1995; 123(10):754-62.
Am Soc Nephrol. 2003; 14(12):3217-32.
Mortensen J, Gomis R, Andersen S, Arner P. 15. Nahman N, Kronenberger J, Sferra T, Clark K. Transcriptional activation of the TGF-b gene by angiotensin II: implications for 23. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin- 16. Siegert A, Ritz E, Orth S, Wagner J. receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.
growth factor receptors by angiotensin II 24. Jacobsen P, Andersen S, Rossing K, Jensen dialysed diabetic patients: a prospective BR, Parving HH. Dual blockade of the renin- 25. Wilmer WA, Hebert LA, Lewis EJ, et al. Remission of nephrotic syndrome in type 1 31. Xue JL, Everson SE, Constantini EG, et al. diabetes: long-term follow-up of patients Peritoneal and hemodialysis: II. Mortality characteristics. Kidney Int. 2002; 61(2):741-6.
26. Mashall S etal, Chronic kidney Disease in 32. Organ Procurement and Transplantation Diabetes Update. Proceedings 2009; 21-28 33. Meier-Kriesche HU, Port FK, Ojo AO, et al. 27. Locatelli F, Pozzoni P, Del Vecchio L. Renal Effect of waiting time on renal transplant outcome. Kidney Int. 2000; 58(3):1311-7.
diabetes and end-stage renal disease. J Am 34. Mange KC, Joffe MM, Feldman HI. Effect of Soc Nephrol. 2004; 15 Suppl 1:S25-9.
the use or nonuse of long-term dialysis on 28. Schwenger V, Zeier M, Ritz E. How can the 35. Kasiske BL, Snyder JJ, Matas AJ, Ellison MD, 29. Koch M, Kutkuhn B, Grabensee B, Ritz E. history of stroke are predictors of death in Original PapersPrevalence of phage types & biotypes among Salmonella Typhi and Salmonella Paratyphi A isolates from Rourkela, Orissa.
Address for communication :
Seshadri S Bhattacharya, Usha Das
Ispat General Hospital, Rourkela, Orissa.
Email: [email protected]
ABSTRACT
fever in India. However, isolation of Salmonella Aim of this study was to highlight the changes in enterica serotype Paratyphi A causing the same prevalence of phage types encountered among disease have been reported with an increasing Salmonella isolates from Rourkela. Besides S. Typhi as the main causative agent of enteric fever, S.Typhi causing enteric fever since 1996, whereas S. Paratyphi A has also been emerging with isolation of S.Paratyphi A causing the same increasing rate as the other causative agent of disease has been encountered in this place since enteric fever from different parts of India including Rourkela. This retrospective study was Phage typing is a major means of epidemiological carried out between September 2005 and August tracing as strains within a particular serotype may 2006 with 1454 patients attending out-patient- be differentiated into a number of phage types, departments (OPD) and wards of Ispat General and may help to define groups of persons who Hospital, Rourkela, India. Phage typing and have been infected with the same strain from the biotyping was performed for randomly chosen same source. Again, combination of biotyping isolates of S. Typhi (N=36) and S. Paratyphi A with phage typing gives a finer discrimination of (N=12). A distinctive change has been noticed in strains in tracing out the source of infection. The the prevalence of phage types compared to their prevalence pattern reported earlier. Phage type epidemiological tracing had been documented 40 was the most commonly encountered phage since 1982 in different parts of India.
among S. Typhi isolates followed by type E1. Phage typing and biotyping of both Salmonella Susceptibility testing was performed for all 112 Typhi and Salmonella Paratyphi A had been isolates of Salmonella including 48 strains chosen reported from Rourkela in 2006 and 2007. There randomly for phage typing and biotyping. Though was a noticeable change in the prevalence pattern 4-5% of Salmonella isolates showed resistance to of phage types encountered among S.Typhi ciprofloxacin, they were highly sensitive to both isolates in 2005-2006 in comparison to the phage a m i n o g l yco s i d e s a n d t h i rd ge n e rat i o n types found in 2004-2005. In this retrospective, cephalosporins. Diversity among the phage types hospital based study, we have highlighted the changes in the prevalence pattern of phage types probably due to the diverse origin of those and biotypes among the Salmonella isolates phages. Salmonella enteric serotype Typhi is the chosen randomly. The susceptibility pattern of most commonly occurring causative agent of Salmonella isolates including the typed strains have also been reported in this communication.
Key words
Materials & methods
Prevalence; Phage typing; Biotypes; Randomly This study was conducted between September chosen; Susceptibility testing; Diversity.
2005 and August 2006. A total of 1454 patients Introduction
attending out-patient departments (OPDs) and Salmonella enteric serotype Typhi is the most wards of Paediatric and Medicine departments of commonly occurring causative agent of enteric Ispat General Hospital , Rourkela, Orissa, suspected of having enteric fever or pyrexia of the patients, 768 were males (52.81%) and 686 unknown origin (PUO) were included in this study. A total of 1454 blood samples were included in Of 1454 patients, 112 were positive for Salmonella this study. Irrespective of repeat sample we have isolates giving a per cent positivity of 7.70. Of 112 taken into account only one sample from each patient. Only positive isolation was considered for Host organism Phage type Biotype No. of isolates the patients having both positive and negative Clinical samples of blood were collected in brain heart infusion broth with sterile precautions and incubated aerobically at 37 C for 48 hours. Three subcultures were done on blood agar, MacConkey agar and Salmonella-Shigella agar and incubated aerobically at 37 C for 18-24 hours. In negative cases subcultures were done for one week.
Isolation of S. Typhi and S. Paratyphi A was Phage types encountered among S. Typhi and S. Paratyphi A isolates in Rourkela between September 2005 and August 2006.
Identification of these two serotypes was established by biochemical and serological testing with factor sera. Antibiotic susceptibility testing was performed by Kirby Bauer disk diffusion method, with the modifications recommended by the National Committee for Clinical Laboratory Standards (NCCLS). Antimicrobials agents tested were ampicillin, co-trimoxazole, chloromycetin, gentamicin, amikacin, ciprofloxacin, cephotaxime Randomly selected strains of both S. Typhi andS. Paratyphi A were sent to the National Susceptibility pattern of S. Typhi and S. Paratyphi Salmonella Phage Typing Centre, Lady Hardinge A isolates in Rourkela between September 2005 and August 2006.
Medical College, New Delhi, India, for phage Salmonella isolates, 92 were S. Typhi strains and remaining 20 were S. Paratyphi A strains. Almost 75 per cent of isolates were from pediatric population, among which 52.38% were boys and Out of 1454 patients, 1052 were children (72.35%) and remaining 402 were adults (27.65%). Among In 2004-2005, the predominant phage type Host organism Phage type Biotype No. of isolates encountered among S. Typhi strains was E1, followed by phage type A (Table 1). In the present study (2005-2006), predominant phage type encountered among S. Typhi isolates was 40, which itself is a rare and exotic phage type in India. Second most common phage type of S. Typhi isolates in this study was E1 and number of Vi-Negative strains was 4 (Table 2). In both the studies mentioned, the predominant phage type found among S. Paratyphi A strains was type 6, Phage types encountered among S. Typhi ans S. Paratyphi A isolates in Rourkela between September 2004 and August 2005.
followed by phage types of either 4 or 1. Most of the phage types of S. Typhi isolates phage type 40, which itself is a rare and exotic belonged to biotype I, except for phage type 40 phage type of S. Typhi in India. It is worth and USV-2. All the phage types of S. Paratyphi A mentioning that two more rare and exotic phage isolates belonged to biotype II (Table 2).
types of multi-drug resistant (MDR) S. Typhi strains, namely type 51 and type 28, caused Ampicillin and chloramphenicol sensitivity among outbreaks in Kolkata and Mumbai respectively,1,12 S. Typhi isolates was found very high in our study, but in case of phage type 40, most of the strains though 40-45% of S. Paratyphi A isolates showed were not multi-drug resistant. Emergence of Vi- resistance to these antimicrobials (Table 3). negative strains among S. Typhi isolates in Isolates of both S. Typhi and S. Paratyphi A showed Rourkela was another important finding during remarkably high susceptibility to gentamicin and amikacin. Resistance to ciprofloxacin was 4-5% among the isolates of S. Typhi and S. Paratyphi A. Till date, not many study-reports are available Susceptibility to cefotaxime and ceftriaxone was regarding phage typing and biotyping of S. very high among the isolates of both S. Typhi and Paratyphi A. A study among the patients (coming from Indian subcontinents) in Kuwait reported that 66% of S. Paratyphi A isolates belonged to Randomly chosen strains of both S.Typhi and S. phage type I. Another study from Nagpur also Paratyphi A for phage typing and biotyping were showed that the prevalent phage type among S. Paratyphi A isolates from the local population was antimicrobials used in our study. Out of 36 isolates type I. The most commonly encountered phage of S. Typhi, only 2 strains showed resistance to type of S. Paratyphi A isolates from Rourkela was type 6, a finding which hardly got any other cephotaxime. Out of 12 strains of S. Paratyphi A contemporary reference in India. From 1992 to randomly chosen for phage typing and biotyping, 2003, commonest biotype of S. Paratyphi A in only 3 strains showed resistance to ampicillin, co- trimoxazole and chloramphenicol. Interestingly, phages of S. Paratyphi A belonged to biotype II. all these 3 MDR strains of S. Paratyphi A belonged S. Typhi strains isolated from Kolkata, Nagpur and Discussion
Phage typing is one of the most important means accounted for 44.4% of S. Typhi isolates and of epidemiological tracing. In 1982-89, the order of frequency of phage types in north and central Susceptibility pattern to ampicillin and India was A, E, O, while in south the second chloramphenicol were very encouraging for onwards , E1 became the most commonly phage was not that much inspiring for S.Paratyphi A type except in south India, where phage type O isolates in this study. In this study, differences in was the predominant type. In 1992, the order of per cent susceptibility between S. Typhi and frequency had become E1, O, A throughout the country. However, there was hardly any report of phage type O from any part of the country since statistically significant (P<0.05), whereas for the rest of the antimicrobials tested, differences in per In our findings of phage types encountered among cent susceptibility were found insignificant S. Typhi strains from Rourkela, E1 was the most (P>0.05). Although 4-5% resistance to commonly occurring phage type in 2004-2005 ciprofloxacin among Salmonella isolates was a matter of concern, very high susceptibility of 2005-2006. One strikingly different finding in those strains to aminoglycosides (gentamicin and 2005-2006 study was the highest occurrence of amikacin) and third generation cephalosporins (cephotaxime and ceftriaxone) was highly encouraging, and can be used judiciously in case Churchill Livingstone, 1984: 456-81.
9. Baron EJ, Peterson LR, Finegold SM. Bailey A diversity among phage types of S. Typhi isolates and Scott s Diagnostic Microbiology. 9 ed. has been noticed, though in case of S. Paratyphi A, St. Louis, Missouri : Mosby, 1994 : 362-85.
mostly phage type 6 was encountered. This 10. Bauer AW, Kirby WM, Sherris JC and Truck diversity of phage types observed in this eastern M. Antibiotic susceptibility testing by a part of India might be due to the diverse origin of standardized single disc method. Am J Clin these phage types. The diversity of origin of these phages again may be due to the migration of 11. National Committee for Clinical Laboratory population to and from Rourkela, an industrial (steel) township, with respect to other parts of the antimicrobial disc susceptibility tests, 6 ed. country.6 Further studies are required regarding the epidemiological tracing especially for the National Committee for Clinical Laboratory exotic phage type 40 of S. Typhi isolates.
References
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