Fatty Kidney

INTRODUCTION
Fatty kidney was first described at 1883, when fat accumulation
at the renal tubule was found on forensic examination of people
who died from diabetic coma

Recently, data from epidemiological stucy shows correlation

between obesity and albuminuria in cases of CKD.
EPIDEMIOLOGY

Approximately 14-30% of people with obesity also have CKD.

The number is concerning, since more people have obesity,

and the number is continuously growing

Obesity is defined by the WHO as people with BMI of > 30

kg/m2
EPIDEMIOLOGY

Another way to give more reliable is the measurement of

waist circumference (WC) and waist-hip ratio (WHR), where
WHR is proven to be more reliable in classification of CKD.

Normal Value Male Female

WC 102 88

WHR 0,9 0,8

Underlying Mechanism
Overweight and obesity is linked to hemodynamic changes,
structural and histopathological alteration, and metabolic and
biochemical changes, which mau result in renal disease, even
if the laboratory findings shows normal renal function.

Adipocytes will produce adipokynes (such as leptin,

adiponektin, tumor necrosis factor-alfa, monocyte
chemoattractant protein-1), converting growth factor-beta
dan angiotensin-II.
Underlying Mechanism

These mechanism will increase renal blood pressure and also

other metabolic changes such as insulin resistance and
diabetes, which will lead to kidney disease and decreased GFR

Obesity will increase sodium reabsorption at the renal

tubules, disrupting the natriuretic pressure, and causes
volume expansion due to symphatetic and RAAS activation
Underlying Mechanism
Activation of the sympathetic nervous system also contributes to
hypertension related to obesity.
Increased levels of sympathetic nerve leptin and its effect on
increasing pressure blood also includes inhibition of the synthesis of
nitric oxide which is a potent vasodilator. Increased endothelin-1
production also occurs in obese people, which contributes to increased
blood pressure and an increase in kidney dysfunction.
Recent research shows that endothelin-1 is increased in patients with
intradialysis hypertension.
Endothelin-1 plays a key role in hypertension in patients with CKD and
may be associated with hypertension in obese patients.
Underlying Mechanism

Adipose tissue accumulation, especially visceral adiposity, causes kidney

compression, and consequently an increase in intrarenal pressure, which leads to
increased extracellular matrix formation in the renal medulla.

Because the kidney is surrounded by the capsule, which has low compliance,
accumulation of extracellular matrix can further worsen intrarenal compression
and increase the hydrostatic pressure of interstitial fluid.

Increased intrarenal pressure of Henle loops and peritubular capillaries (vasa recta)
reduces fluid flow through renal tubules which cause sodium reabsorption.
Underlying Mechanism
Another important factor in the pathophysiology of fatty kidneys is
"lipotoxicity" which corresponds to the needs exposed by non-adipose
exacerbations, such as skeletal muscle, pancreatic beta cells
(pancreatic islets), myocardium and kidneys. In the case of "excess
nutrition / excess nutrition", reserves of fatty acids in the excess tissue
need to increase oxidation compensation.

Increased levels of fatty acids lead to the production and release of

several substances harmful to cells, such as lipid peroxidation products
and triglycerides, which can be used for apoptosis and fibrosis in non-
adipose tissue
Underlying Mechanism

Obesity in rare cases can cause nephrotic syndrome. Obesity is also

shown to be a risk factor for CKD in glomerulopathic patients.

Weight loss, either by diet or through bariatric surgery, may improve

the proteinuria.

The relationship between obesity, metabolic syndrome and

nephrolithiasis has been approved in several studies, most of which are
compared with elevated serum uric acid levels in obese individuals.
Obesity and Fatty Kidney
Obesity is the main clinical feature of metabolic syndrome, which further includes
other renovascular risk factors such as dyslipidemia, hypertension, and insulin
resistance.

Increased free fatty acid deposits in the cortical kidneys from the accumulation of
triglycerides contribute directly to hyperglycemia in metabolic syndrome and type
2 diabetes through increased gluconeogenesis, impaired glucose use and increased
renal insulin resistance.

The contribution of fatty kidney to hypertension is partly due to the direct effect of
increased external physical pressure on the kidneys by accumulation of ectopic fat
which leads to activation of intra-renal local components of the renin angiotensin
aldosterone system (RAAS) and the sympathetic nervous system.
Obesity and Fatty Kidney
Hilar fat deposits and increased retroperitoneal pressure have the greatest impact
where the kidneys do not have protective fibrous capsules, compressing blood
vessel bundles which include arteries, veins and lymphatic systems and renal
neurons.

Central obesity can increase intra-abdominal and retroperitoneal pressure, and

transmitted directly to the renal parenchyma, further contribute directly to
hypertension and CKD.

RAAS activation in obesity contributes to the stimulation of the sympathetic

nervous system and also hyperleptinemia, which lead to further alteration of focal
glomerular sclerosis and function change of the kidney
Diagnosis

Ectopic kidney fat deposit in fatty kidney is an advanced stage

characterized by impaired kidney function and albuminuria on
laboratory examination.

The diagnosis of fatty kidney is often analogous in people with obesity,

metabolic syndrome, and type 2 diabetes mellitus, but specific
diagnoses require radiological examinations such as ultrasonography,
CT scan or MRI.
Radiological examination does not specifically describe renal ectopic fat
deposits, except when there is a mass / tumor containing fat.

It is hoped that a new focus on the kidneys will help develop and improve the
radiological diagnostic criteria of fatty kidney as has been done for the
examination of fat in the liver and other organs (epicardial fat). In the past 20
years, tissue lipid levels can be measured with proton magnetic resonance
spectroscopy (PMRS) which is accurate enough for clinical assessment.35
Hepatic triglycerides are closely correlated with central obesity in individuals
who are biopsied for liver steatosis.36 Measurement of non-invasive
triglycerides in the heart , liver and muscle have been done in vivo.37,38
Measurements of renal cortical triglycerides with PMRS have been explained
and correlated with biopsy values ​assessed enzymatically.39
Diagnosis
Ectopic kidney fat deposit in fatty kidney is an advanced stage
characterized by impaired kidney function and albuminuria on
laboratory examination.

The diagnosis of fatty kidney is often analogous in people with obesity,

metabolic syndrome, and type 2 diabetes mellitus, but specific
diagnoses require radiological examinations such as ultrasonography,
CT scan or MRI.

Radiological examination does not specifically describe renal ectopic fat

deposits, except when there is a mass / tumor containing fat. Further
research is needed.
Diagnosis
Recently, tissue lipid levels can be measured with proton
magnetic resonance spectroscopy (PMRS)

Hepatic triglycerides are closely correlated with central obesity in

individuals who have liver steatosis proven from biopsy

Measurement of non-invasive triglycerides in the heart , liver

and muscle have been done in vivo.
Measurements of renal cortical triglycerides with PMRS have been
explained and correlated with biopsy values ​assessed enzymatically.
 Management
Pharmacological Management
• No clinical data on the reduction of renal ectopic fat with pharmacological therapy, but there are
studies on management to reduce ectopic fat deposits in other organs with overlapping
pathophysiology.

• Several SGLT 2 inhibitors have shown reduction of ectopic fat in the liver and epicardium in type 2 DM
patients.

• A study evaluating by MRI examination, ipragliflozin reduced epicardial fat accumulation in DM type 2.

• Remoglijlozin patients in type 2 DM with NAFLD reduced F 1-4 Sscores between 5-17% and increase
alanine transferase by 32-42% .

• Lusoegliflozin and canagliflozin significantly reduce liver fat and show improvement in NAFLD
Management
Non-pharmacological Management
• Observational studies in obese people shows that obesity alone can cause kidney dysfunction and
kidney damage even without diabetes or hypertension.

• Lifestyle modifications including calorie restriction and increased physical activity has proven a risk
reduction for CKD events by 30%, although it does not affect CVD events.

• In a meta-analysis of experimental studies in obese and CKD patients, interventions aimed at reducing
body weight showed a significant reduction in blood pressure, glomerular hyperfiltration, and
proteinuria.

• Bariatric surgical interventions are recommended for CKD and ESRD patients, including
patients indicated for kidney transplantation who running dialysis
 CONCLUSION
Extra ectopic and intra-renal fat deposits create a different clinical entity called fatty
kidney which is similar to non-alcoholic fatty liver disease.

Both contribute to systemic diseases, such as hyperglycemia, hypertension, and

inflammatory cytokines as well as local effects that cause disease in the organs
themselves.
The incidence of obesity has increased worldwide and is an important risk factor for
kidney disease.

There are evidences that obesity alone can lead to the development of kidney
disease, including chronic kidney disease, glomerulopathy and nephrolithiasis.

Consultation about the risks from obesity and promotion of healthy lifestyle,
including proper nutrition and exercise, can help prevent obesity and fatty kidney.