Chronic kidney disease

Background

The South African prevalence of CKD is not well known but in the USA, about 4% of the population has a GFR of less than 60 ml/min, and 0.1% have end-stage renal failure.¹ Developing world prevalence data is scanty, with one study of 8110 people 40 to 60 years old from both rural and urban sites finding a prevalence of CKD of 10.7% with 2.4% having an eGFR of less than 60.² This amounts to over six million people with CKD in South Africa, and possibly 200 000 with ESRF with one estimate³ of more than 20 000 deaths annually due to lack of access to renal replacement therapy. With current levels of health care financing, and the public sector political emphasis on prevention and primary care, it is only possible to offer renal replacement therapy to 10-20 out of every 200 people with CRF. This means that over 90% of people with ESRF can only be palliated; this is very clearly an instance where prevention is far superior to attempted cure.

Chronic kidney disease – identification and slowing of progression

Managing chronic kidney disease entails first identifying the disease stage, and then tailoring therapy to the patient and the stage.⁴

Stage	GFR	Description
1	>90	Diagnosis and treatment if possible, CVS risk reduction, slow progression
2	60-90	Evaluate progression (GFR, protein excretion)
3	30-60	Manage complications of progressing kidney disease
4	15-30	Evaluate and prepare for renal replacement therapy if appropriate, discuss palliative strategies if not
5	<15	Proceed to dialysis/transplant once uraemic if accepted on a renal replacement programme

Most of the interventions to slow disease progression are self-evident, and focus on life-style modification:

• Stop smoking
• Deal with obesity – aim for ideal body weight
• Salt restriction – less than 5g/day
• In diabetics, attempt to tighten glycaemic control (HbA1C <6.5%) but remember that tight control produces a more brittle patient in the presence of renal impairment, and oral agents become progressively more likely to precipitate life-threatening hypoglycaemia as renal function falls off.
• Protein restriction – about 0.7g/kg/day.
• Blood pressure control, ideally with an ACE inhibitor, with the aim of reducing proteinuria to less than 0.5g/day.⁵ Target blood pressure should be less than 130/80, and even lower than this (125/75) if proteinuria is more than 1g/day. Check the creatinine after two weeks, and if it has risen by more than 20%, consider stopping the ACE inhibitor as it may be the cause for that rise.

Diabetes and CKD

Insulin resistance can be demonstrated in non-diabetics with CKD even before a major drop in GFR, renal gluconeogenesis is a recognised component of glucose metabolism, and insulin is partially metabolised in the kidney. All of this makes managing glucose control in CKD non-trivial. A few points:

• As GFR declines, patients need less and less exogenous insulin, until it can often be stopped entirely. “Well controlled” glucose in a clinic book should be a source of some concern, as it often presages presentation with severe hypoglycaemia when the kidney function deteriorates a little further.
• Avoid long acting sulponylureas like glibenclamide, particularly when GFR < 60. Glimepiride can be used with caution in low dosage (e.g. 1 mg/day) perhaps even down to a GFR of 30⁶, but the evidence for this is weak. If monitoring of GFR is likely to be poor, rather avoid sulphonylureas altogether.
• Metformin is also cleared less completely in CKD, and should be used with extreme caution if GFR < 60 (max dose 500 mg 2x/d) and avoided if GFR < 30 ml/min.⁷

Perspective – ACE inhibitors in chronic kidney disease

ACE inhibitors and angiotensin receptor blockers are traditionally considered the agents of choice in the management of proteinuria in CKD, and there is a widely held belief that ‘more is better’ with these agents, with a postulated pleiotropic effect beyond mere blood pressure control. (For BP control, saturable enzyme kinetics means that dose escalation beyond conventional upper limits achieves little.)

A systematic review⁸ confirmed the beneficial effects of ACE-I and ARBs over other antihypertensives (overall RR for development of ESRF 0.87, CI 0.75-0.99) but noted that effect size was largest for small studies, less for larger studies, and non-existent for ALLHAT, which recruited patients with no or only mild kidney disease. For the endpoint of doubling of serum creatinine, the effect was even less impressive, not reaching statistical significance (overall RR 0.71, CI 0.49-1.04) and in fact showed a non-significant increased risk in diabetics. For the endpoint of change in GFR, ACE-Is and ARBs were also no better than other antihypertensives. The authors’ conclusion was that when other antihypertensives reduced BP to the same degree as ACE-Is and ARBs, renoprotective effects were similar.

Renal replacement therapy

Apart from the financial limitations on this process, there are also limits in terms of availability of donors, and human resource limitations in terms of staff time. Renal replacement therapy needs to be seen as a combination of initial dialysis (if necessary) and then transplantation. To simply place sick individuals on long-term dialysis is not a viable option, as the machines would soon be over-utilised. New patients cannot enter the program if those on dialysis are not being transplanted, and in many countries other than the USA, the proportion of all patients with kidney disease who end up getting renal replacement therapy is quite small.

Chronic peritoneal dialysis allows more patients to be treated, but it costs about the same as haemodialysis and has similar mortality (10-20% per year)⁹ After transplantation, the need for ongoing immunosuppression is costly, and quite rigorous for the patient in terms of follow-up visits.

Renal replacement therapy is highly effective for many patients; the difficulty is trying to decide who is most likely to benefit.

As a general rule, it is advisable to consider as many of the issues listed below prior to raising the issue of dialysis with the patient. Raising expectations that the health system is unable to meet is distressing to the patient and erodes confidence in you as a caregiver.

Does the patient really want the procedure?

Sometimes, older patients attend for an explanation, or even just confirmation of something they already suspect (and accept). In one’s natural enthusiasm to talk about therapy, one may lose sight of the fact that the patient actually doesn’t want treatment.

Is the diagnosis correct?

(i.e. exclude potentially reversible causes – medication and myeloma are two possibilities).

Logistics

If the patient lives far away from a dialysis centre and lacks regular transport, the process may not be feasible. This is rationing by limiting access, and is clearly undesirable. Without a better social support service, however, it seems to be current reality in many parts of the country. Check also that the patient doesn’t have relatives closer to the centre with whom he/she could stay for an extended period.

Social support.

The dialysis/transplant process is rigorous, and the more genuine family support that there is for an individual, the more likely it is to succeed.

Personal commitment and strength.

This is difficult to judge, but as a surrogate, difficulties with compliance in the past should raise concerns.

Hepatitis B status.

Although Hepatitis B positive individuals are transplanted, they seem to wait a long time for a kidney, and as a group outcome is a little worse. They also need separate machines for dialysis.

Education.

An Italian study showed that people with greater education exposure had better outcomes after transplant.¹⁰

Renal transplantation

Discussing transplantation may seem odd in a text geared to resource constraints. In practice, most health care systems seem to have a peculiar amalgam of the frugal and the gloriously expensive, perhaps reflecting the historical development of health care, and the fact that the tools of health economics have only recently become operational.

If a public service transplantation programme exists, then it should provide open access to all citizens. In practice, it is more likely that a person living closer to the transplantation unit will gain access. This reflects the difficulties of transport and follow-up experienced by individuals living far away, as well as a possible reluctance of health care staff in more remote areas to refer their patients.

The peri-transplant period involves work-up and evaluation of patient and potential donors, and close follow-up after the procedure, and for this reason most potential recipients should expect to spend several months in either the transplant unit itself or the city in which it is situated.

Success of transplantation for an individual unit is not always easy to ascertain. Some representative rates are shown in the table. (Clearly, the more selected the series, the better he results will look.)

Relative contraindications to transplantation include:

• Malignancy
• Severe liver disease: cirrhosis or chronic active viral hepatitis (B or C)
• Severe lung disease: COPD or bronchiectasis
• Psychosocial instability or serial non-adherence to treatment
• Active infections such as TB or HIV (unless stable on ART)
• Other systemic illnesses – e.g. severe cardiomyopathy, severe peripheral vascular disease
• Morbid obesity

(Age is also sometimes used as a cut-off – e.g. >60 years, or >50 if diabetic; in some programmes this is not an issue.)

Erythropoietin

In the context of the expenditure scales for dialysis/transplant, the use of erythropoietin as part of the strategy to normalise haemoglobin is probably appropriate. The correct dose and dose frequency is unclear, with one review¹¹ suggesting that weekly therapy was as effective as thrice weekly treatment.

---

1. El Nahas AM, Bello AK. Chronic kidney disease: the global challenge. Lancet. 2005;365:331-40 ↩

2. George JA, Brandenburg JT, Fabian J, et al and the H3Africa Consortium. Kidney damage and associated risk factors in rural and urban sub-Saharan Africa (AWI-Gen): a cross-sectional population study. Lancet Glob Health. 2019 Dec;7(12):e1632-e1643. doi: 10.1016/S2214-109X(19)30443-7. PMID: 31708144; PMCID: PMC7033368. ↩

3. (Calculated from the ‘two plane loads per week’ figure in: Moosa MR, Meyers AM, Gottlich E, Naicker S. An effective approach to chronic kidney disease in South Africa. S Afr Med J. 2016 Jan 21;106(2):156-9. doi: 10.7196/SAMJ.2016.v106i2.9928. PMID: 26821893. ↩

4. Perazella MA, Reilly RF. Chronic kidney disease: a new classification and staging system. Hosp Physician. 2003;Mar:18-23 ↩

5. Zandi-Nejad K,  Brenner BM. Strategies to retard the progression of chronic kidney disease. Med Clin N Am. 2005;89:489-509 ↩

6. Ioannidis I. Diabetes treatment in patients with renal disease: is the landscape clear enough? Word J Diab. 2014;5:651-658. DOI: 10.4239/wjd.v5.i5.651 ↩

7. Inzucchi SE, Lipska KJ, Mayo H, et al. Metformin in patients with Type 2 diabetes and kidney disease. A systematic review. JAMA. 2014;312(24):2668-2675. doi:10.1001/jama.2014.15298 ↩

8. Casas JP, Chua W, Loukogeorgakis S, et al.  Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: sytematic review and meta-analysis. Lancet. 2005;366:2026-33 ↩

9. Pastan S, Bailey J. Dialysis therapy. N Engl J Med. 1998;338:1428-37 ↩

10. Miceli M, Di Lallo D, Perucci CA. Absence of economic barriers does not reduce disparities in the access to renal transplantation: A population based study in a region of central Italy.  J Epidemiol Comm Health. 2000;54:157-8 ↩

11. Cody J, Daly C, Campbell M, et al. Frequency of administration of recombinant human erythropoietin for anaemia of end-stage renal disease in dialysis patients (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd ↩

Was this article helpful?

1 out Of 5 Stars

1 rating

5 Stars		0%
4 Stars		0%
3 Stars		0%
2 Stars		0%
1 Stars		100%

5 Submit

Send Feedback

How can we improve this article?

Please submit the reason for your vote so that we can improve the article.

Submit