Assessment of Kidney Assessment of Kidney functionfunction Challenges and

opportunities

George MoturiPhysician/Nephrologist

Aga Khan University Hospital Nairobi

25.04.2015

Road mapRoad map

• Introduction

• Why do you want to know the kidney function?

• Challenges: assessing kidney function in devolved HCS

• Opportunities: assessing kidney function in devolved in HCS

• Integrating e-medicine in assessing kidney function

• Conclusions

Road mapRoad map

• Introduction

• Why do you want to know the kidney function?

• Challenges in assessing kidney function in devolved HCS

• Opportunities in a assessing kidney function devolved in HCS

• Integrating e-medicine in assessing kidney function

• Conclusions

2020

3. Secretion of erythropoitin 1,25-dihydroxy vitamin D3 (vitamin D activation) renin prostaglandin

Major Functions of the Kidneys

2. Excretion of metabolic products foreign substances (pesticides,

chemicals etc.) excess substance (water, etc)

1. Regulation of: body fluid osmolarity and volume electrolyte balance acid-base balance blood pressure

What is kidney disease?What is kidney disease?

• Acute kidney injury (AKI)Acute kidney injury (AKI)

• Acute kidney disease (AKD)Acute kidney disease (AKD)

• Chronic kidney disease (CKD)Chronic kidney disease (CKD)

• No kidney disease (NKD)No kidney disease (NKD)

Definition of CKDDefinition of CKD

Structural or functional abnormalities of the kidneys for >3 months ( ≤ 3 months), as manifested by either:

1. Kidney damage, with or without decreased GFR, as defined by

• pathologic abnormalities• markers of kidney damage

• urinary abnormalities (proteinuria)• blood abnormalities (renal tubular syndromes)• imaging abnormalities

• kidney transplantation2. GFR <60 ml/min/1.73 m2, with or without kidney

damage

NKF-K/DOQI

CKDCKDdeathdeathCKDCKDdeathdeath

ComplicationsComplicationsComplicationsComplications

Screening for CKD

risk factors:diabetes

hypertensionage >60

family historyUS ethnic minorities

CKD riskreduction;

Screening forCKD

Diagnosis& treatment;

Treat comorbid

conditions;Slow

progression

Estimateprogression;

Treatcomplications;

Prepare forreplacement

Replacementby dialysis

& transplant

NormalNormalNormalNormal IncreasedIncreasedriskrisk

IncreasedIncreasedriskrisk

KidneyKidneyfailurefailureKidneyKidneyfailurefailureDamageDamageDamageDamage GFRGFR GFRGFR

11.3 m11.3 m5.6%5.6%

7.7 m7.7 m7.7 m7.7 m3.8%3.8%

0.3 m0.3 m0.2%0.2%

Conceptual Model for CKD

How do you assess kidney How do you assess kidney function?function?

Answer- Glomerular filtration Answer- Glomerular filtration raterate

Glomerular filtration rate does Glomerular filtration rate does not spell etiology of kidney not spell etiology of kidney

disease. disease. What does?What does?

•Urinalysis

•Urinary protein excretion

•Radiologic studies

•Kidney biopsy

The quagmire of The quagmire of kidney diseasekidney disease

Largely asymptomatic

Mitchell AJKD 2006

Frequency of GFR monitoring per year

NICE 2014

Road map

• Introduction

• Why do you want to know the kidney function?

• Challenges in assessing kidney function in devolved HCS

• Opportunities in a assessing kidney function devolved in HCS

• Integrating e-medicine in assessing kidney function

• Conclusions

CKD is a Public Health Problem

• CKD is common

• CKD is harmful

• We have treatment

Adjusted Hazard Ratio for Death from Any Cause, CardiovascularEvents, and Hospitalization among 1,120,295 Ambulatory Adults,

According to the Estimated GFR

Alan et al NEJM 2004

Stevens NEJM 2006

Road mapRoad map

• Introduction

• Why do you want to know the kidney function?

• Challenges: assessing kidney function in devolved HCS

• Opportunities in a assessing kidney function devolved in HCS

• Integrating e-medicine in assessing kidney function

• Conclusions

What are the hurdles to diagnosing Kidney diseases in Africa?

Naicker et al. NDT 2010; 25: 649-650

Glomerular filtration rate (GFR)Glomerular filtration rate (GFR)

The physiological mechanism of glomerular filtration is generally well understood

A more complex issue, however, is the measurement of GFR in clinical practice and especially the definition of “normal” renal function

Normal value : Men - 130 ml/minFemale - 120 ml/min

Screening for CKD is not a Screening for CKD is not a preserve of the Nephrologistpreserve of the Nephrologist

The large number of patients who have CKD, together with the number of people at increased risk for it,

requires primary care providers, as well as specialists in areas other than nephrology, to increase their

familiarity with the use of GFR estimates

Assessing function - Assessing function - ToolsTools

• Urine output• GFR• Urinalysis• Novel biomarkers• Imaging • Biopsy

Production of creatinineProduction of creatinine

•Non-enzymatic breakdown product of phosphocreatine in muscle

•Produced at a relatively constant rate based on age, gender,race, and muscle mass

•Not affected by diet

Factors Affecting Creatinine Generation

Acute changes in kidney function are not immediately apparent.

Creatinine excretion is due not only to filtration (90%–95%) by the kidney but also to secretion (5%–10%) by the proximal tubule. If the patient with advanced CKD takes a substance that blocks tubular secretion of creatinine (eg, trimethoprim, cimetidine, cefoxitin), the serum creatinine level will increase abruptly, but the actual GFR will not change

Extra-renal elimination of creatinine occurs.

.

Other Limitations of Creatinine-Other Limitations of Creatinine-Based eGFRBased eGFR

Stevens NEJM. 2006

Cystatin CCystatin C

Produced by all nucleated cells at a constant rate and freely filtered at the glomeruli

Minimally affected by diet, gender, ethnicity, age and muscle mass

Affacted by glucocorticoids and thyroid hormone

Early detection of acute renal failure by serum cystatin C

Serum cystatin C is a useful detection markerof ARF, and may detect ARF one to two days earlier than creatinine.

Stefan et al. KI 2004:66:1115–1122

Creatinine Creatinine Equations Equations 1. Cockroft-Gault equation – 1973

2. Original MDRD Study equation - 1999 3. “Reexpressed” MDRD Study equation for standardized – 2005

4. CKD-EPI equation - 2009

Cystatin C Equations Cystatin C Equations

1. CKD –EPI cystatin C equation not adjusted for age, sex, and race

2. CKD – EPI cystatin C equation adjusted for age, sex, and race

3. CKD – EPI cystatin C and creatinine equation adjusted for age, sex, and race

Performance of Three Equations for Estimating Glomerular Filtration Rate (GFR)

Inker NEJM 2012

The combined creatinine–cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease

Road map

• Introduction

• Why do you want to know the kidney function?

• Challenges in assessing kidney function in devolved HCS

• Opportunities: assessing kidney function in devolved HCS

• Integrating e-medicine in assessing kidney function

• Conclusions

Where do we start?Where do we start?

•National Vs regional kidney disease registries

•Standardized assessment of kidney function

•Referral pathways for kidney diseases

•Structured awareness campaigns

Measurement of Serum Measurement of Serum Creatinine – Current Status and Creatinine – Current Status and

Future GoalsFuture Goals• Creatinine measurement should be based on the isotope dilution-

mass spectrometry (IDMS) method

• Standardisation of serum creatinine measurements to IDMS

• Jaffe Assay (since 1886) – should be abandoned

Peake and Whiting Clin Biochem Rev 2006

Urine protein :Quantitative Urine protein :Quantitative measurementmeasurement

24 hour collection of urine for protein normal excretion is <150 mg/24 hour

Spot urine protein/urine creatinine ratio

Microalbuminuria: 30 – 300mg/24hrs

Macroalbuminuria: ≥ 300mg/24hrs

Screening for Urine proteinScreening for Urine protein

Dipstick: Gives green color, does not check for light chains

Negative– 10 mg/dlTrace – 15-25 mg/dl1-2+ – 30-100 mg/dl3+ – 300 mg/dl

Sulfosalicylic acid: white precipitate

Day-to-today clinical Day-to-today clinical situationssituations

Determining the exact GFR is rarely necessary. Instead, it is important to determine whether renal function is stable or getting worse or better—which can usually be accomplished by monitoring serum

creatinine value alone.

Road map

• Introduction

• Why do you want to know the kidney function?

• Challenges in assessing kidney function in devolved HCS

• Opportunities in a assessing kidney function devolved in HCS

• Integrating e-medicine in assessing kidney function

• Conclusions

Health in CloudHealth in Cloud

eHealth

• Fully integrated national health system – None in developing countries

mHealth

• WelTel SMS System• ChildCount+Register• Changamka(finance)

Ecosystem for mobile health

ICT Sector World Bank 2011

eTargets in Kidney diseaseseTargets in Kidney diseases

• Mobile updates

• Mobile reminders

• Mobile eGFR

Road map

• Introduction

• Why do you want to know the kidney function?

• Challenges in assessing kidney function in devolved HCS

• Opportunities in a assessing kidney function devolved in HCS

• Integrating e-medicine in assessing kidney function

• ConclusionsConclusions

Take away Take away MessagesMessages

• Often assessment of kidney function is the only indicator of renal impairment

• Structural defects can be present despite normal or even supra-normal kidney function

Take away Messages…

• Complete assessment kidney status will require GFR, Urinalysis, Imaging, +/- biopsy

• Reporting of renal function should be routine in all laboratories and if possible individualized

• We should and/or must assess kidney function of all our clients

• eHealth and mHealth can enhance kidney health in our population

Frequency of GFR monitoring per year

NICE 2014