Essay on Diabetic Nephropathy

This essay provides a detailed discussion on the pathophysiology and nursing management of diabetic nephropathy based on a case study. Learn about the causes, metabolic pathways, and hemodynamic imbalances of diabetic nephropathy.

Running head: ESSAY ON DIABETIC NEPHROPATHY
ESSAY ON DIABETIC NEPHROPATHY
Name of the Student
Name of the University
Author’s Note:

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Introduction:
Chronic kidney disease or CKD is a global burden on the healthcare system of the various
government (Jha et al. 2013). Study have suggested that almost 1.7 million Australians are
affected by the chronic kidney disease (Australian Institute of Health and Welfare 2019). This
signifies that the around one out of 10 Australians are affected by the Chronic kidney disease
(Australian Institute of Health and Welfare 2019). Hence, as a result chronic kidney disease puts
a heavy burden on the Australian health care system in term of financial budget and provision of
health care facility. By term chronic kidney disease it can be stated that it is a kidney condition
which gets worse over the year as the disease progress. By long time, the person has to have the
condition for at least 3 months to be called it a chronic kidney disease (Jha et al. 2013). There are
many different types of chronic kidney disease are prevalent among the individuals. However,
risk factors for the different type of chronic kidney disease are common among the different
types of chronic kidney disease. Diabetes and old age are most prevalent among the different
types of chronic kidney disease (Hill et al. 2016). Therefore, the purpose of this essay is to
provide a detailed discussion on the patho- physiology and nursing management of a chronic
kidney disease based on a case study provided below.
The case study that will be presented in this essay is of a Caucasian male. The real name of the
patient will be omitted in the case study to protect the privacy and keep the confidentiality of the
patient. Thus, the patient will be referred here as Mr. X is a 60 year old male who has long
history of the Type 2 Diabetes Mellitus. Mr. X has been suffering from diabetes mellitus for
more than 15 years. During these years of his suffering from diabetes, he was treated with anti-
diabetic agents in his earlier year and he has been using insulin for the last five years. In addition
to that Mr. X has a history of smoking and he used to smoke quite heavily (2 pack of cigarette

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per day). The reason of his visit to the emergency department was oedema, dysponea and
nocturia. At the time of his visit to the emergency department, he was in good condition overall
and he was oriented and conscious. At that time, the patient’s blood pressure was 160/ 110 mm
Hg and his heart rate was 81 beats per minute. His blood analysis revealed glucose level of 200
mg/ dl, urea level of 52 mg/ dl, creatinine level of 1.2 mg/ dl, uric acid level of 5.3 mg/ dl, and
cholesterol level of 313 mg/ dl. In addition to this, his albumin level was 1.9 g/ dl and total
protein level was 4.4 g/ dl. Furthermore, the patient’s antibodies, thyroid hormones, PSA, and
viruses (HIV, hepatitis B and C) were normal.
Discussion:
From the case study of Mr. X presented above it can be deduced that the patient is suffering from
diabetic nephropathy and the high blood pressure is a co- morbid factors of his chronic disease
condition which is diabetic nephropathy (Heras et al. 2011). Therefore in the following sections,
patho- physiology of diabetic nephropathy will be discussed along with brief nursing
management for diabetic nephropathy.
Patho- physiology of Diabetic nephropathy:
The most common cause of end stage renal failure in the modern world is diabetic nephropathy
(DN). In a diabetic person with retinopathy, high blood pressure and decreasing glomerular
functions in the apparent lack of urinary tract infection, other renal diseases or a cardiac
insufficiency, and persistent proteinuria (> 0.3 g/24 h) is defined to be present (Klemetti et al.
2015). During the first 13 -20 years of diabetes, the yearly occurrence of diabetic nephropathy
increases rapidly to only to decrease sharply afterwards. The diabetic nephropathy affects a
smaller proportion of Type 2 diabetic patients of Caucasian origin and affects up to 33 per

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cent of Type 1 diabetic patients. Moreover, 30 per cent of diabetic patients in renal alternation
treatment have higher prevalence of type 2 diabetes (De Zeeuw et al. 2013). Diabetic
nephropathy usually follows a well-lined clinical pathway, beginning with azotaemia
proteinuria, and ultimately resulting in end stage renal disease or ESRD with micro- albuminuria.
Until overt proteinuria starts, there are different functional retinal changes, such as renal hyper
perfusion, hyper filtration, and increased macromolecular capillary permeability. These
alterations are complemented by the development of ultra- structural modifications including
glomerular cell membrane thickening, glomerular hypertrophy, and mesangial expansion,
followed by the development of glomerulosclerosis and TBF or tubule- interstitial fibrosis. The
thickness of the basement membrane is a pathological marker of diabetes (Sun et al. 2013). In
two years after diagnosis, thickness is detectable and ten years later the majority of patients are
diagnosed thickening. Mesangial enlargement might seem to take place after glomerular sub-
structure membrane thickening, even though this might not be the genuine chain of events as
alterations in substructural membrane thickness are functionally easier to identify than in
mesangium. The accumulation of the matrix is the majority of mesangial expansion rather than
tissue increase. Mesangial enlargement is much more intimately connected to the diagnostic
results of structural lesions that characterize Diabetic nephropathy (Park et al. 2013).
Multiple hormonal and metabolic facilitators have been involved both systematically and
regionally in the altered glomerular function of diabetes. These are: growth hormone,
hyperglycemia, renal prostaglandin, glucagon, and atrial natriuretic peptide. The interplay
of hemodynamic and metabolic factors in renal micro circulation have suggested that Diabetic
nephropathy occurs, but processes through which such factors lead to glomerular mesangal

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expansion and eventual glomerulosclerosis (Sharma and Sharma 2013) have not yet been fully
explained in a sub set of susceptible patients.
Metabolic pathways:
Hyperglycemia: Hyperglycemia does not totally responsible for the possibility of microvascular
diabetes, and it is less compelling, particularly in humans, for the simple causation
relationship of hyperglycemia and renal disease. Non-diabetic human donor’s organ
which transplanted into a diabetic recipient tends to develop typical lesions of diabetic
glomerulopathy, but the frequency of lesion development in different kidneys varies widely,
irrespectively of their blood glucose history (Chilelli, Burlina and Lapolla 2013). Hyperglycemia
is therefore apparently necessary in humans, but it is not enough to cause kidney failure.
Metabolic abnormality of AGE creation and sorbitol acquisition interplay and lead to the
development of diabetic complications. For instance, both of the sorbitol path way are clearly
interacted by oxidative stress (Chilelli, Burlina and Lapolla 2013).
Non-enzymatic glycosylation: The pathogenesis of diabetic complications could be involved
through non enzymatic glycosylation three possible mechanisms. (a) AGE's change the way
ligands on the extra cellular matrix involve transduction signal. (b) AGEs change the amount of
soluble signals, like hormones, cytokines, and free radicals, by means of developed cellular
receptor glycosylation finishes (Donate-Correa et al. 2015). (c) Intermediate intracellular
glycosylation can directly affect the protein function of target tissue, with intermediate glucose,
fructose and metabolic pathway. Increased glomerular membrane glycosylation of the basement
may raise the degree of cross linking di- sulfide between collagen parts by an increased
sulphydryl group oxidation (Satirapoj 2013). Diabetic nephropathy is susceptible to glycemic

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control and the genetic disposition of kidney condition has been explained by inherited
differences in the ability to detoxify enzymatically advanced intermediate end products such as
3- deoxyglucosone (Satirapoj 2013).
The polyol pathway: The main path way substrate in diabetes is glucose and is converted to
sorbitol by the enzyme aldose reductase with NADPH oxidization followed by sorbitol
dehydrogenase oxidation to fructose with NAD+ reductions (Van Dam et al. 2013). The papilla,
gloral epithelial cells, distal tubular cells and mesangial cells contain aldose reductase is
present in the renal tube. The renal medulla cells in the neuron, in reaction to the high salinity of
the medullary interstitium, appear to be involved with the creation of sorbitol, an organic
osmolyte, from glucose. Sorbitol will also help osmotic stress prevention. The aldose reductase
inhibitor ponalrestat was found to cause a decrease of the glomerular filtration rate in a short
term study of normoalbuminuric insulin dependent patients. Though, clinical studies were scarce
and the results were largely unfinished (Van Dam et al. 2013).
Protein Kinase C System: Protein Kinase C System is belongs to family of 12 iso- enzymes
which are broadly distributed among the protein group of threonine and serine. In the Protein
Kinase C System main regulatory activators is daicylgycerol which activates the K, Na – ATPase
(Zenker, Ziegler and Chrast 2013). In the studies it has been reported that the exposure of high
glucose in the endothelial cells or renal glomeruli activates the Protein Kinase C System. It has
also been found out that among the different Protein Kinase C System isoforms, beta isoform of
Protein Kinase C System is particularly affected to the high glucose system in the system. The
activation of the Protein Kinase C System involves in the de- novo formation of the
diacylglycerol which is a like effect of the oxidative stress. In this scenario, presence of probucol
or Vitamin E inhibits the activation of the Protein Kinase C System. Additionally, the activation

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of Protein Kinase C System also linked with the MAP or mitogen-activated protein kinase
induction. MAP or mitogen-activated protein kinases gets activated through the dual
phosphorylation on the response of the extracellular stimuli (Zhang et al. 2014). There has also
been a presence of link between prostaglandin and Protein Kinase C System. In a study
conducted among the rats it has been found that the presence of high level blood glucose in the
glomeruli increase the phospholipase A2 activity. On the other hand, presence of calphostin acts
as a Protein Kinase C System inhibitor which inhibits the activation phospholipase A2 activity.
From the information presented in the fore mentioned sentences, it can be stated Protein Kinase
C System is chief among the signaling molecule in case of vascular patho- physiology of the
diabetic nephropathy (Wada and Makino 2013).
Biochemical abnormalities of extracellular matrix: in the diabetic nephropathy, excessive
accumulation occurs in the mesangial matrix and the glomerular basement membrane. There are
several growth factors and cytokines which have been identified by the scientist responsible for
the accumulation matrix production. In this context, transforming growth factor β or TGF – β
particularly plays a pivotal role (Park et al. 2013). Transforming growth factor β is able to inhibit
and stimulate the various kinds of extracellular matrix. From the study, it can also be deduced
that the transforming growth factor β, mRNA and expression of protein tend to increase in the
streptozotonic induced renal cortex or glomeruli (Park et al. 2013). Recent study in this area also
suggests that the transforming growth factor β acts as a mediator for the tissue injury caused by
hyperglycemia (Park et al. 2013).
Hemodynamic pathway:

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In case of diabetic nephropathy, various hemodynamic imbalances occurs in the glomerulus
which includes pressures and flows. In this scenario, it has been reported that it is directly
responsible for the glomerulosclerosis as well as proteinuria. It can has been reported that the
elevated intra- glomerular pressure is present in case of diabetic nephropathy. This intra-
glomerular pressure can be present in the absence of systematic hypertension as well. This
systematic pressure transmission can be explained by the efferent versus afferent arteriolar
resistance pressure (Toth-Manikowski and Atta 2015). This increase intra- glomerular pressure
leads to an elevated matrix and mesangial cell production which in turn leads to the thickening of
membrane through the increment in capillary and arterioral tension. In this scenario, epithelial
surfaces might get damaged due to the shear forces and physical stress. This damage in the
epithelial surfaces might lead to the turbulence in the arteries in case of the systematic
hypertension. It has also been reported that this mechanism is responsible for the induction of the
expression in the mesangial cells. It has also been reported that there is a relation between the
Protein Kinase C dependent System and mitogen-activated protein kinase levels which gets
amplified by the presence of the high blood glucose level in the system (Pappachan et al. 2013).
Genetic Pathway:
Genetic plays a role in the incidence of the chronic kidney disease like diabetic nephropathy. It
has been reported in the studies that the genetics influences the incidence of the diabetic
nephropathy. Studies have reported that the genetic influence plays a role in the insulin
dependent or independent diabetes among the diabetic nephropathy patients (Harjutsalo and
Groop 2014). It can also be stated that the genetic disposition like elevated arterial pressure
might be contributing factor of the nephropathy among the diabetic patients. Studies have been
conducted to identify the gene loci which are responsible for and increase the chance of diabetic

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nephropathy among the individuals (Harjutsalo and Groop 2014). In this case, the gene group of
renin- angiotensin have gained particular attention owing to the reason it plays in case of sodium
metabolism, high blood pressure, and renal hemodynamics. Even though no consistent and
strong link has not been found among the genetic factors and type 1 and type 2 diabetes group.
Studies focused in this area has reported that identification of particular and specific gene group
is particularly difficult due to the diverse nature of etiology diabetic nephropathy (Harjutsalo and
Groop 2014).
Endothelial dysfunction:
In human body vascular endothelium are responsible for the platelet function, hemostasis, renal
mesangial cells, propagation of vascular smooth muscle and, micro- vascular permeability, and
vessel tone (Maezawa, Takemoto and Yokote 2015). Academic investigations conducted in this
area have reported that the vascular endothelium dysfunction is intricately related with the
incidence of diabetic nephropathy among the patients. It has also been reported that the
endothelial dysfunction might be related with the early onset of the micro- albuminuria
development (Maezawa, Takemoto and Yokote 2015).
Therefore, from the above discussion it can be stated that insights related patho- physiology
diabetic nephropathy has been discovered in many areas. It can also be stated that the
hemodynamic, cellular factors and metabolic factors are all intricately related to the onset of the
diabetic nephropathy and plays a vital role in the progression and development of diabetic
nephropathy among the individuals.
Nursing Management of diabetic nephropathy:

9ESSAY ON DIABETIC NEPHROPATHY
One of the most prevalent approach for the management of the diabetic nephropathy is the multi-
disciplinary approach towards patients. Recent studies have presented the fact that multi-
disciplinary approach is really helpful for the management of the co-morbid factors associated
with diabetic nephropathy as well as the slow the progression of the disease (Johns et al. 2015).
Studies have also presented the fact that the provision of the multidisciplinary approach will
optimize the management of the chronic kidney disease (Martinelli et al. 2019). From the various
studies presented in this area have suggested that the multi- disciplinary team will consist of
nephrologist, endocrinologist, clinical nurse specialist, pharmacist, dietitian, and podiatrist
(Johns et al. 2015). It has been reported in the studies that the multi- disciplinary approach
enhance the outcomes of the patient management which includes re-hospitalization rates and
mortality, reducing costs, adherence to treatment, increasing health literacy, self-care abilities,
improving patients' functional status, and quality of life (Martinelli et al. 2019).
Conclusion:
Therefore, from the above discussion, it can be stated that chronic kidney disease is a global
burden on the health care system and it is increasing day by day. Understanding the patho-
physiology of this disease will help to better understand the disease, so than better health care
service can be provided to the patient. Hemodynamic pathway, cellular factors and metabolic
factors are all intricately related to the onset of the diabetic nephropathy and plays a vital role in
the progression and development of diabetic nephropathy. Multi- disciplinary nursing
management can be really helpful to provide optimal service to the patient suffering from
chronic kidney disease like diabetic nephropathy.

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Hill, N.R., Fatoba, S.T., Oke, J.L., Hirst, J.A., O’Callaghan, C.A., Lasserson, D.S. and Hobbs,
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