Significance, definition, classification and risk factors of chronic kidney disease in South Africa.

Renal dysfunction or chronic kidney disease (CKD) is found in 10% of the global population and is classified into five stages according to the estimated glomerular filtration rate (eGFR). No matter where a patient lives, estimation of the GFR is mandatory for decision-making and obtained by the simple measurement of a serum creatinine level. The objective of diagnosing CKD lies in its future prevention, early detection and proper treatment, which will prevent or delay functional deterioration. Primary hypertension (PH) occurs in 25% of South Africa (SA)s black population and is the putative cause of stage 5 CKD in 40 - 60% of these patients. Moreover, in this group, stage 5 CKD occurs at a relatively young age (35 - 45 years) compared with other population groups in whom stage 5 CKD resulting from PH usually occurs between 60 and 70 years of age. In the cohort study, PH has been found in 12 - 16% of black school learners (mean age 17 years) compared with 1.8 - 2% of other ethnic groups (mixed race, Asian, white). End-stage renal failure (ESRF) is the fifth most common cause of death in SA, excluding post-traumatic cases. In addition, undiagnosed or poorly controlled PH is a potent risk factor for other cardiovascular disease (CVD), e.g. congestive cardiac failure, myocardial infarction, stroke. Significant protein is also associated with CVD and protein >1 g/d is a significant risk factor for ESRF.

Chronic kidney disease.

It is known that, for many reasons, general practitioners(GPs) find renal disease difficult to diagnose, understandand treat. The terms chronic kidney disease (CKD) andglomerular filtration rate (GFR), representing the renalfunction equation, have been introduced to clarify someof these difficulties. Unfortunately, even these pivotal concepts remaineither unknown or poorly understood by the majority of GPs in SouthAfrica (SA). CKD is often not recognised because there are no specificsymptoms, and not diagnosed or only diagnosed at an advanced stage.Tests for CKD are, however, simple and freely available.

Paediatric chronic kidney disease.

Doctors use various guidelines on paediatric chronic kidney disease (CKD) for managing their patients according to the availability of resources. As with adolescent and adult patients, CKD in children can also progress to end-stage renal failure - the time course being influenced by several modifiable factors. Decline in renal failure is best categorised in stages, which determine management and prognosis. Staging is based on three categories, i.e. cause, glomerular filtration rate and proteinuria. Early diagnosis of CKD allows for the institution of renoprotective treatment of modifiable factors and treatment to prevent the development of complications. The two most important modifiable factors that can be treated successfully are hypertension and proteinuria. The objective of this article is to provide information on the diagnosis and treatment of CKD in children. Early identification and treatment of modifiable risk factors of CKD decreases the burden of disease and delays or prevents the need for renal replacement therapy.

Important causes of chronic kidney disease in South Africa.

In hypertensive patients without chronic kidney disease (CKD) the goal is to keep blood pressure (BP) at ≤140/90 mmHg. When CKD ispresent, especially where there is proteinuria of ≥0.5 g/day, the goal is a BP of ≤130/80 mmHg. Lifestyle measures are mandatory, especiallylimitation of salt intake, ingestion of adequate quantities of potassium, and weight control. Patients with stages 4 - 5 CKD must be carefullymonitored for hyperkalaemia and deteriorating kidney function if angiotensin-converting enzyme (ACE) inhibitors or angiotensin IIreceptor blockers (ARBs) are used, especially in patients >60 years of age with diabetes or atherosclerosis. BP should be regularly monitoredand, where possible, home BP-measuring devices are recommended for optimal control.Guidelines on the use of antidiabetic agents in CKD are presented, with the warning that metformin is contraindicated in patients withstages 4 - 5 CKD.There is a wide clinical spectrum of renal disease in the course of HIV infection, including acute kidney injury, electrolyte and acid-basedisturbances, HIV-associated glomerular disease, acute-on-chronic renal disease and side-effects related to the treatment of HIV.

Important complications of chronic kidney disease.

The complications of chronic kidney disease (CKD) are dyslipidaemia, hyperkalaemia, metabolic acidosis, anaemia, and bone and mineraldisorders. Dyslipidaemia may be treated with low-density lipoprotein-lowering agents. Statins are ineffective in stages 4 and 5 CKD, but areindicated for preventing the progression of disease in the earlier stages. Chronic acidosis has recently been shown to be a risk factor in theprogression of CKD renal dysfunction. Therefore, treatment is mandatory. Practically, this should consist of 1 - 2 heaped teaspoons of sodiumbicarbonate 2 - 3 times per day, which is an inexpensive and safe therapy that does not raise the blood pressure in spite of the increased sodiumlevel. Target levels of haemoglobin, according to international guidelines, are between 10 g/dL and 12 g/dL. The serum phosphate level is raisedin stage 4 CKD, and especially in stage 5 CKD, which is associated with coronary carotid and other vascular calcifications and may result inischaemic heart disease, myocardial infarction and stroke. A raised parathyroid hormone level (secondary hyperparathyroidism) is also a majorrisk factor for cardiovascular disease and is associated with increased hypertension and resistance to the treatment of CKD-associated anaemia.

Drugs and the kidney.

This article on drug nephrotoxicity is detailed, as it is important to be fully aware of renal side-effects of drugs with regard to prevention andearly diagnosis in order to manage the condition correctly. Many therapeutic agents are nephrotoxic, particularly when the serum half-life isprolonged and blood levels are raised because of decreased renal excretion. Distal nephrotoxicity is markedly enhanced when the glomerularfiltration rate (GFR) is reduced and is a particular threat in elderly patients with so-called 'normal' creatinine levels. In patients of 45 - 55 years of age theGFR is reduced by about 1 mL/min/year, so that an otherwise healthy person of 80 may have an estimated GFR (eGFR) of <60 mL/min or <50 mL/min,i.e. stage 2, 3 or 3b chronic kidney disease (CKD). Furthermore, other effects related to kidney dysfunction may be seen, e.g. worsening of hypertensionwith the use of non-steroidal anti-inflammatory drugs, increased bruising or bleeding tendency with aspirin, and hyponatraemia hypertensionacidosis with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Digoxin is contraindicated in stage 3 CKD, even ina reduced dosage. Other drugs can cause the direct formation of kidney stones, e.g. topiramate (used in the prophylaxis of resistant migraine).Levofloxacin (Tavanic) can cause rupture of the Achilles tendon and other tendons.Radiocontrast media must be used with care. Occasionally, strategies to prevent acute kidney insufficiency cause irreversible CKD,especially in patients with diabetes and those with myeloma who have stage 4 - 5 CKD. Gadolinium in its many forms (even the newerproducts) used as contrast medium for magnetic resonance imaging is best avoided in patients with stages 4 and 5 CKD.

Salvage reconstruction with vascularized fibular strut graft fusion using posterior approach in the treatment of severe spondylolisthesis.

STUDY DESIGN: One case is reported in which a failed anterior fusion for Grade 4 spondylolisthesis was treated with a vascularized fibular strut graft using a posterior approach. OBJECTIVES: To demonstrate the applicability of this technique for salvage cases or patients with systemic conditions that may decrease the success of more standard techniques. SUMMARY OF BACKGROUND DATA: Surgical stabilization of spondylolisthesis through posterior approach with a fibular strut graft has been previously described. A vascularized strut graft can be used in the treatment of spondylolisthesis and may have applicability in those patients with underlying disease that may impair the use of more standard techniques or in salvage reconstruction. METHODS: With the patient under general anesthesia, through a posterior approach S1 and L4 were decompressed. The fibula with its vascularity intact was harvested and anastomosed with the superior gluteal artery and vein. The fibular strut was placed into the space formed by reaming between L5 and S1. Ilial autograft was used to augment the posterior fusion. After the procedure the patient was placed in a hip spica cast. RESULTS: At the 2-year follow-up the patient has incorporation of the graft, with no evidence of fracture and no significant progression of anterior slip. CONCLUSION: A vascularized fibular strut graft is a feasible alternative in the treatment of severe spondylolisthesis. No complications were encountered in the involved patient. Future application may include salvage reconstruction of failed arthrodesis or in individuals with systemic conditions that may impair graft incorporation using more standard techniques.

Revisiting the role of physical activity and exercise in the treatment of type 2 diabetes.

There is tremendous potential for improving glycemic control, insulin sensitivity, and cardiovascular risk factors through increased physical activity in individuals with Type 2 diabetes. The demonstrated effects of structured endurance exercise on select outcomes compare favorably with those of typical pharmacological treatment modalities. Adherence to these types of program is problematic, however. We know less about the expected effects of lifestyle-based physical activity. Preliminary results require further investigation, given the apparent acceptability of these programs in this population, however. The effects of resistance training on cardiovascular risk factors to date likely limit its application as an adjunctive therapy for individuals with Type 2 diabetes. The question is no longer "can exercise/physical activity benefit the individual with Type 2 diabetes?" The answer is yes. Future research needs to refine questions regarding type, dose, and magnitude of effects of physical activity (and its subcategory exercise) on glycemic control, insulin sensitivity, and on risk factors for cardiovascular disease within the context of program acceptability and feasibility.

Lithogenic risk factors in normal black volunteers, and black and white recurrent stone formers.

OBJECTIVE: To compare lithogenic risk factors in normal black volunteer men (BN), male black stone formers (BSF) and male white recurrent stone formers (WSF); in addition, the differential diagnoses in the stone formers were compared to determine if the causes of renal stones differed in the two groups. SUBJECTS AND METHODS: The study included 22 BN, 22 consecutive BSF and 122 consecutive WSF seen over a 10-year period. Each subject was assessed by a thorough medical history, dietary analysis and a full serum and urinary biochemical evaluation. RESULTS: Although the WSF were significantly more overweight (P<0.001) and obese (P<0.001) than the BSF, neither group had values significantly different from those of their respective normal populations. There was no significant difference in serum levels of Ca, phosphorus, ionised Ca, calcitriol and alkaline phosphatase in BSF and WSF, but levels of parathyroid hormone tended to be (P<0.1) and calcitriol was significantly higher in BSF than WSF (P<0.03). The BSF urinary excretion levels tended to be more like that of the WSF, with the following pattern present; BN

Microangiopathic hemolytic anemia as a complication of diabetes mellitus.

A mature-onset diabetic patient who developed microangiopathic hemolytic anemia (MHA) is presented. Although numerous causes of hemolysis are reported in the literature, MHA is a rare complication of diabetes. The proposed mechanism of hemolytic anemia is thought to be related to the abnormal formation of cell membranes in the diabetic environment. The ratio of cholesterol to phospholipid in the core of the membrane is altered in diabetics; as a result, the red blood cell wall becomes rigid and nondeformable. The abnormal cells becomes disrupted as they circulate through the microangiopathic blood vessels. The mechanism of action of the antiplatelet agents is to enhance cell membrane compliance. With improved cell-wall compliance, one can expect a reduction in hemolysis, as occurred in our patient. The literature on diabetes mellitus-related microangiopathic hemolytic anemia is reviewed.

Lithogenic risk factors in the urine of black and white subjects.

OBJECTIVE: To identify biochemical and dietary factors which may play a role in the low incidence of stone formation in the black South African population. SUBJECTS AND METHODS: The study included 31 semiurbanized black and 29 urbanized white subjects. The protocol and modern laboratory techniques used to assess recurrent stone formers were followed. Urinary sodium, potassium, creatinine, calcium, phosphate and urate levels were measured, and urinary citrate, oxalate and cystine assessed. RESULTS: Black subjects ate a diet significantly higher in sodium (P < 0.04); there was no difference in serum levels but urinary sodium was significantly higher (P < 0.001) in black than in white subjects. Urinary potassium, calcium, citrate, phosphate and cystine were all significantly lower in black than in white subjects (P < 0.001 for the first four and P < 0.03 for cystine). CONCLUSION: Certain intrinsic factors in South African black subjects may account for their lower frequency of stone formation than in white subjects. Of these, the very low urinary calcium, decreased urinary cystine and different interactions between sodium and calcium/cystine are probably important.

Clinical experience with Repotin, a locally produced recombinant human erythropoietin, in the treatment of anaemia of chronic renal failure in South Africa.

OBJECTIVE: To evaluate the efficacy and safety of Repotin, a locally produced recombinant human erythropoietin (rHuEPO), in the treatment of the anaemia of chronic renal failure (ACRF). DESIGN: The study consisted of two multicentre non-randomised open stages. SETTING: Renal units at several teaching hospitals in South Africa. PARTICIPANTS: Haemodialysis patients with haemoglobin (Hb) levels less than 8.0 g/dl were recruited. The first stage examined 26 patients during a 12-week period in which the dose of intravenous rHuEPO was adjusted according to haematological response. In the second stage 27 patients were stabilised with intravenous rHuEPO and then maintained at a Hb level above 8.0 g/dl by subcutaneous administration for up to 1 year. OUTCOME MEASURES: In both stages, outcome was measured by clinical examination, blood pressure, full haematological parameters and blood chemistry. RESULTS: In stage 1, all patients responded to therapy with a statistically significant increase in Hb from geometric means of 6.28 g/dl to 8.50 g/dl (geometric SDs of 1.17 and 1.20 respectively). The doses used ranged from 25 IU to 125 IU/kg (average 47.1). In the second stage, Hb levels reached a mean of 8.06 g/dl (SD 0.9) and were maintained at target range with an average dose of 55.5 IU/kg three times a week. Apart from changes in serum iron, ferritin (associated with increased haematopoiesis) and potassium, there were no significant alterations in blood chemistry. The incidence of adverse events reported during the 12-month second stage was no greater than that reported for other forms of rHuEPO therapy. CONCLUSION: Repotin is a safe and effective rHuEPO preparation for the treatment of ACRF.

Indapamide (Natrilix): the agent of choice in the treatment of recurrent renal calculi associated with idiopathic hypercalciuria.

OBJECTIVE: To compare the hypocalciuric and potential side-effects of hydrochlorothiazide (HCT) to indapamide (IND; a thiazide-like drug) in patients with idiopathic hypercalciuria. PATIENTS, SUBJECTS AND METHODS: Twelve patients with recurrent renal calculi and renal hypercalciuria were studied using a randomized double-blind cross-over protocol. In addition, because the side-effects of HCT are attenuated using small doses, the hypocalciuric effect of 12.5, 25 and 50 mg daily was assessed in six normal subjects. RESULTS: There was a significant reduction in urinary calcium excretion using both agents, with a mean (SD) of 6.06 (2.68) and 3.37 (2.00) mmol/24 h using IND, and 5.58 (1.98) and 3.93 (2.35) mmol/24 h using HCT, before and after treatment (P < 0.05). The treatment was not sufficiently prolonged to assess adequately all the side-effects of either agent but both produced a similar decrease in serum potassium, whilst HCT significantly increased the mean (SD) serum urate levels, from 0.34 (0.09) to 0.43 (0.08) mmol/L (P < 0.01). There was also a significant decrease in mean (SD) urinary citrate excretion in those receiving HCT, from 1.41 (1.05) to 1.00 (0.71) mmol/24 h (P < 0.001), but not in those receiving IND, from 1.19 (0.71) to 1.18 (0.79) mmol/24 h. Although there was a hypocalciuric effect with doses of 12.5 and 25 mg HCT, it was sub-therapeutic when compared with the dose of 50 mg. CONCLUSION: At a daily dose of 2.5 mg, IND is at least as effective as 50 mg HCT in controlling hypercalciuria. Because of its safety profile and lack of effects on urinary citrate excretion, this agent should be the preferred therapy for patients with idiopathic hypercalciuria and recurrent renal calculi.

Long-term effects of potassium citrate therapy on the formation of new stones in groups of recurrent stone formers with hypocitraturia.

OBJECTIVE: To compare stone formation rates before (as total rates and during remote periods) and after therapy with potassium citrate in patients with hypocitraturia. PATIENTS AND METHODS: The study comprised 15 patients with hypocitraturia only (Group I) and 12 patients with hypocitraturia associated with other abnormalities (Group II), all of whom were recurrent stone formers. Their urine chemistry, including citrate, was measured before and after treatment. RESULTS: In both groups, the urinary citrate concentration increased significantly to within normal limits during therapy with potassium citrate (P < 0.005). The rate of total stone formation in patients in Group I decreased significantly from 0.7/year before to 0.13/year after treatment (P < 0.005). The corresponding remote stone formation rate before (0.88/year) was significantly greater than the rate after treatment (0.13/year; P < 0.005; follow-up 4.6 +/- 1.9 years). Patients in Group II showed a similar striking decrease in total stone formation rate, from 1.2/year to 0.08/year after treatment (P < 0.005). The corresponding remote stone formation rate (1.66/year) before was significantly greater than that after treatment (0.08/year; P < 0.005; follow-up 4.1 +/- 1.6 years). There was a remission rate of 93% for stone formation over the complete follow-up. CONCLUSION: Potassium citrate appears to be the drug of choice in the long-term treatment of patients with hypocitraturia as it not only decreases the rate of stone formation but also maintains normal citrate levels in the urine.